Effect of mda-7/IL-24 gene transfection on the growth of hepato-cellular carcinoma cells
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《中华医药杂志》英文版
1 Nantong Cancer Hospital Affiliated to Nantong University,Nantong,Jiangsu Province 226361, China
2 Affiliated Hospital of Nantong University,Nantong, Jiangsu Province 226001,China
Correspondence to ZHANG Yi-xin, Nantong Cancer Hospital Affiliated to Nantong University,Nantong, Jiangsu Province 226361,China
Tel:+86-0513-86712002,Fax:86-0513-86571201,E-mail:zyxhxb@hotmail.com
[Abstract] Objective In order to study the effect of mda-7/IL-24 gene on the growth of hepatocellular carcinoma Hep3B cell.Methods The mammalian expression recombination pcDNA 3.1-mda-7/IL-24 was constructed. pcDNA 3.1-mda-7/IL-24 and pcDNA 3.1 was transfected into Hep3B cell respectively. G418 was used to screen the transformants. The expression of mda -7 gene and protein were detected by RT-PCR and immunohistochemistry.Results The results showed that the growth rate of G418 resisant Hep3B cells with the expression of mda-7 /IL-24 was more quick than that of vector transfected Hep3B cells and untransfected Hep3B cells.Conclusions It was concluded that mda-7/IL-24 gene can inhibit the growth rate of hepatocellular carcinoma cells and as a good candidate of tumor suppressor gene. It has a wide appliable prospect.
[Key words] mda-7/IL-24 gene; cell transfection; gene expression; apoptosis
Melanoma differentiation-associated gene-7 (mda-7)/IL-24 was identified by a combination of recombinant fibroblast interferon (IFN-b) and the protein kinase C activator mezerein (MEZ) subtraction hybridization by Fisher in 1995[1~3]，encoded a protein of 23.8 kD,Southern blot analysis documented that mda-7/IL-24 was an evolutionary conserved gene and a novel cytokine gene with the inhibitory effect on the growth of cancer cells. Mda-7 is a unique multifunctional cytokine in the IL-10 family and may have potent antitumor utility in a clinical setting[9].Mingzhong Zheng,et al.have defined a tumor-selective cytotoxic bystander role for secreted IL-24 protein and identified a novel receptor-mediated death pathway in breast cancer cells, wherein the related cytokines IL-24 and IL-10 exhibit antagonistic activity[10]. Mda-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma[11].
MATERIALS
Hepatocellular carcinoma Hep3B cell, the mammalian expression recombination pcDNA 3.1, Lipofectamin, Trizol reagent come from Invitrogen company. Mda-7/IL-24 come from Shanghai Kaiyue Bio-Technology Co,Ltd. Cell line were cultured in high glucose DMEM supplemented with 10% fetal bovine serum (FBS) at 37 ℃ in a humidified incubator containing 5% CO2 95% in air. G418, DMEM, fetal bovine serum come from GIBCO Co,Ltd.PCR and RT-PCR kit come from TaKaRa Biotechnology (Dalian) Co., Ltd. (TaKaRa Dalian), Escherichia coli strain DH5 come from gene Co., Ltd.
METHODS
Construction and Identification of the Mammalian Expression Recombination pcDNA 3.1-mda-7/IL-24 For construction of pcDNA 3.1-mda-7/IL-24, PCR products and pcDNA 3.1 subcloned at XbaI and XhoI sites.The products was extracted with phenol method. After purification, the products transform to DH5α bacterium strain with CaCl2 ice incubation method,to select single clone of DH5α to extract plasmid obtained to gain the plasmid with mda-7.
Mda-7/IL-24 gene transfection and cell clone select according to the manufacturer's instructions of reagent kit of GIBCO Co., Ltd, the plasmid with mda-7.Mda-7/IL-24 gene was transfected into Hep3B cell by Lipofectamin to take pcDNA 3.1 transfected without the plasmid and Hep3B not transfected as control. After transfection of 48 hour, G418 was used to screen the transformants.
Growth Curves
Cells including control cultured 24 hour without serum,then cells were seeded in 24-well tissue culture plates (2×104 cells/well), every other 24 hour,selected 3 plates cells to digest to count cells number and calculated the mean,last 7 days, and the growth curves were drawn.
RT-PCR
Cells were plated in 24-well plates, transfected and cultured as described, the cells were harvested at 48 h after transfection. Total RNA was isolated by Trizol Reagent (GIBCO) according to the manufacturer's protocol of Shanghai Bio-Technology Co,LtD.Primers used in PCR were designed according to the reported IL-24 cDNA sequence. The products of PCR were analyzed on 10 g/L agarose gel electrophoresis.
Immunohistochemical Analysis
The cell lines were plated on collagen-coated coverslips in 24-well plates, the anti- mda-7 mAb was diluted 1∶2000, according to the manufacturer's protocol of immunohistochemistry, the cells were visualized on microscope by using the ×40 objective.
RESULTS
Recombination pcDNA 3.1-mda-7/IL-24 Identification
Human mda-7/IL-24 cDNA was directionally cloned into pcDNA 3.1 to produce pcDNA 3.1-mda-7/IL-24 and Escherichia coli strain DH5 plasmid were co-transfected to Hep3B cell to construct the recombinant,carrying mda-7/IL-24 gene, by intracellular homologous recombinant. The genomes were analyzed to confirm the recombinant structure.After transfection,choosed 10 recombinant clones,picked out XbaI and XhoI sites,after excise with XbaI and XhoI enzyme, 680 bp and 55 kb slices were positive clones,others were negative clones.
Figure 1 Recombined plasmid pcDNA 3.1-mda-7 identification
M1: λDNA/Hind Ⅲ marker;M2:marker 2000; 1:after excise with enzyme pcDNA3.1/mda-7 showed two positive clones 0.68 and 5.7kb；2：pcDNA 3.1 with unoccupied vector
Expression of mRNA of mda-7/IL-24 Gene
pcDNA 3.1 vector and the recombinant of pcDNA 3.1-mda-7/IL-24 were directionally transfected intoHep3B cell by Lipofectamin. G418 was used to screen the transformants. Total RNA was isolated by Trizol Reagent. Assayed the expression of mRNA of mda-7/IL-24gene with RT-PCR.The result showed that there was a ribbon of 680 bp in mda-7/IL-24 clone but not in pcDNA 3.1 with unoccupied vector and Hep3B cell without transfection.
Figure 2 Expression of mRNA of Mda-7/IL-24 gene in Hep3B cell
M：Marker;1: positive control;2： Hep3B cell with transfection of mda-7/IL-24gene;3:Hep3B cell with transfection of pcDNA 3.1;4：Hep3B cell without transfection
Expression of mda-7/IL-24 Gene in Immunohistochemical Assay
Figure 3 Expression of mda-7 of Hep3B cell without transfection
Figure 4 Expression of mda-7 of Hep3B cell with transfection of pcDNA 3.1
Figure 5 Expression of ,mda-7/IL-24 gene Mda-7/IL-24 Gene affect Hep3B Cell Growth
Figure 6 Mda-7/IL-24 gene affect Hep3B cell growth
After transfection, pcDNA3.1 with unoccupied vector slightly,affect Hep3B cell growth but after transfection of pcDNA 3.1/mda-7/IL-24, Hep3B cell growth slowed down.
Mda-7/IL-24 gene affect Hep3B cell growth, Hep3B cell with transfection of mda-7/IL-24 gene，grew slower than which with pcDNA3.1 with unoccupied vector.
DISCUSSION
Hepatocellular carcinoma were one of the most common incident cancer in China,especially in our city.At present,there was no better method than surgical excision and chemo- and radio-therapy. In the future,a new therapeutic strategy incorporating clinical evidence, molecular biology, and organ replacement needs to be established for the treatment of liver cancer. [4]. Melanoma differentiation-associated gene-7 (mda-7/IL-24 was identified by a combination of recombinant fibroblast interferon (IFN-b) and the protein kinase C activator mezerein (MEZ) subtraction hybridization by Fisher in 1995[5,6]. Mda-7/IL-24,resulted in growth suppression and apoptosis in a broad-spectrum of cancer cell types,in contrast,mda-7/IL-24 does not elicit deleterious effects in normal cells. [7,8]. Wang CJ, et al.confirmed selectively induction of apoptosis and growth suppression by the mda-7/IL-24 gene with replication-incompetent adenovirus vector in human hepatocellular carcinoma cell line HepG2[12].We constructed the mammalian expression recombination pcDNA 3.1-mda-7/IL-24. pcDNA 3.1-mda-7/IL-24 and pcDNA 3.1 was transfected into Hep3B cell respectively. G418 was used to screen the transformants. The expression of mda -7 gene and protein were detected by RT-PCR and immunohistochemistry.We succeed in transfecting pcDNA 3.1-mda-7/IL-24 into Hep3B cell and constructed the liver cancer cell line with highly expression of mda-7/IL-24. According to growth curves,we could see after transfection of pcDNA 3.1/mda-7/IL-24, Hep3B cell growth slowed down and Hep3B cell was inhibited. It was concluded that mda-7/IL-24 gene can inhibit the growth rate of hepatocellular carcinoma cells and as a good candidate of tumor suppressor gene. It has a wide appliable prospect.Our test would play a significant role in researching the mechanism of the apoptosis of liver cancer with transfected mda-7/IL-24.Our test would also offer test data for mda-7/IL-24 gene therapy.
Funding: Nantong Science and Technology Administration (No. S2019)
REFERENCES
1. Sauane M, Gopalkrishnan RV et al. Mda-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev,2003,14(1):35-51.
2. Madireddi MT, Su ZZ et al.Mda-7, a novel melanoma differentiation associated gene with promise for cancer gene therapy. Adv Exp Med Biol, 2000,465:239-61.
3. Jiang H, Su ZZ,et al. The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci U S A, 1996, 93(17):9160-5.
4. Kamohara Y, Kanematsu T.Treatment of liver cancer: current status and future prospectives.Gan To Kagaku Ryoho,2000,27(7):987-992.
5. Lebedeva IV, Su ZZ et al.The cancer growth suppressing gene mda-7 induces apoptosis selectively in human melanoma cells.Oncogene, 2002,21(5):708-18.
6. Su ZZ, Lebedeva IV et al. Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant liomas in a p53-independent manner. Oncogene, 2003,22(8):1164-80.
7. Caudell EG, Mumm JB et al.The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol, 2002, 168(12):6041-6.
8. Mhashilkar AM, Schrock RD et al.Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy. Mol Med, 2001,7(4):271-82.
9. Chada S, Sutton RB, Ekmekcioglu S, Ellerhorst J, Mumm JB, Leitner WW, Yang HY, Sahin AA, Hunt KK, Fuson KL, Poindexter N, Roth JA, Ramesh R, Grimm EA, Mhashilkar AM. DA-7/IL-24 is a unique cytokine--tumor suppressor in the IL-10 family. Int Immunopharmacol, 2004,4(5):649-67.
10. Mingzhong Zheng, Dora Bocangel, Blair Doneske, Abner Mhashilkar, Rajagopal Ramesh, Kelly K. Hunt, Suhendan Ekmekcioglu, R. Bryan Sutton, Nancy Poindexter, Elizabeth A. Grimm and Sunil Chada. Human interleukin 24 (MDA-7/IL-24) protein kills breast cancer cells via the IL-20 receptor and is antagonized by IL-10. Cancer Immunol Immunother,2006,19,[Epub ahead of print].
11. Ishikawa S, Nakagawa T, Miyahara R, Kawano Y, Takenaka K, Yanagihara K, Otake Y, Katakura H, Wada H, Tanaka F. Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer. Clinical Cancer Research, 2005,11:1198-1202.
12. Wang CJ, Xue XB, Yi JL, Chen K, Zheng JW, Wang J, Zeng JP, Xu RH. Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2 by replication-incompetent adenovirus vector. World J Gastroenterol, 2006,12(11):1774-9.
(Editor Jaque)(ZHANG Yi-xin1，HUANG Jian-)
2 Affiliated Hospital of Nantong University,Nantong, Jiangsu Province 226001,China
Correspondence to ZHANG Yi-xin, Nantong Cancer Hospital Affiliated to Nantong University,Nantong, Jiangsu Province 226361,China
Tel:+86-0513-86712002,Fax:86-0513-86571201,E-mail:zyxhxb@hotmail.com
[Abstract] Objective In order to study the effect of mda-7/IL-24 gene on the growth of hepatocellular carcinoma Hep3B cell.Methods The mammalian expression recombination pcDNA 3.1-mda-7/IL-24 was constructed. pcDNA 3.1-mda-7/IL-24 and pcDNA 3.1 was transfected into Hep3B cell respectively. G418 was used to screen the transformants. The expression of mda -7 gene and protein were detected by RT-PCR and immunohistochemistry.Results The results showed that the growth rate of G418 resisant Hep3B cells with the expression of mda-7 /IL-24 was more quick than that of vector transfected Hep3B cells and untransfected Hep3B cells.Conclusions It was concluded that mda-7/IL-24 gene can inhibit the growth rate of hepatocellular carcinoma cells and as a good candidate of tumor suppressor gene. It has a wide appliable prospect.
[Key words] mda-7/IL-24 gene; cell transfection; gene expression; apoptosis
Melanoma differentiation-associated gene-7 (mda-7)/IL-24 was identified by a combination of recombinant fibroblast interferon (IFN-b) and the protein kinase C activator mezerein (MEZ) subtraction hybridization by Fisher in 1995[1~3]，encoded a protein of 23.8 kD,Southern blot analysis documented that mda-7/IL-24 was an evolutionary conserved gene and a novel cytokine gene with the inhibitory effect on the growth of cancer cells. Mda-7 is a unique multifunctional cytokine in the IL-10 family and may have potent antitumor utility in a clinical setting[9].Mingzhong Zheng,et al.have defined a tumor-selective cytotoxic bystander role for secreted IL-24 protein and identified a novel receptor-mediated death pathway in breast cancer cells, wherein the related cytokines IL-24 and IL-10 exhibit antagonistic activity[10]. Mda-7/IL-24 status was a significant prognostic factor in lung adenocarcinoma, not in lung squamous cell carcinoma[11].
MATERIALS
Hepatocellular carcinoma Hep3B cell, the mammalian expression recombination pcDNA 3.1, Lipofectamin, Trizol reagent come from Invitrogen company. Mda-7/IL-24 come from Shanghai Kaiyue Bio-Technology Co,Ltd. Cell line were cultured in high glucose DMEM supplemented with 10% fetal bovine serum (FBS) at 37 ℃ in a humidified incubator containing 5% CO2 95% in air. G418, DMEM, fetal bovine serum come from GIBCO Co,Ltd.PCR and RT-PCR kit come from TaKaRa Biotechnology (Dalian) Co., Ltd. (TaKaRa Dalian), Escherichia coli strain DH5 come from gene Co., Ltd.
METHODS
Construction and Identification of the Mammalian Expression Recombination pcDNA 3.1-mda-7/IL-24 For construction of pcDNA 3.1-mda-7/IL-24, PCR products and pcDNA 3.1 subcloned at XbaI and XhoI sites.The products was extracted with phenol method. After purification, the products transform to DH5α bacterium strain with CaCl2 ice incubation method,to select single clone of DH5α to extract plasmid obtained to gain the plasmid with mda-7.
Mda-7/IL-24 gene transfection and cell clone select according to the manufacturer's instructions of reagent kit of GIBCO Co., Ltd, the plasmid with mda-7.Mda-7/IL-24 gene was transfected into Hep3B cell by Lipofectamin to take pcDNA 3.1 transfected without the plasmid and Hep3B not transfected as control. After transfection of 48 hour, G418 was used to screen the transformants.
Growth Curves
Cells including control cultured 24 hour without serum,then cells were seeded in 24-well tissue culture plates (2×104 cells/well), every other 24 hour,selected 3 plates cells to digest to count cells number and calculated the mean,last 7 days, and the growth curves were drawn.
RT-PCR
Cells were plated in 24-well plates, transfected and cultured as described, the cells were harvested at 48 h after transfection. Total RNA was isolated by Trizol Reagent (GIBCO) according to the manufacturer's protocol of Shanghai Bio-Technology Co,LtD.Primers used in PCR were designed according to the reported IL-24 cDNA sequence. The products of PCR were analyzed on 10 g/L agarose gel electrophoresis.
Immunohistochemical Analysis
The cell lines were plated on collagen-coated coverslips in 24-well plates, the anti- mda-7 mAb was diluted 1∶2000, according to the manufacturer's protocol of immunohistochemistry, the cells were visualized on microscope by using the ×40 objective.
RESULTS
Recombination pcDNA 3.1-mda-7/IL-24 Identification
Human mda-7/IL-24 cDNA was directionally cloned into pcDNA 3.1 to produce pcDNA 3.1-mda-7/IL-24 and Escherichia coli strain DH5 plasmid were co-transfected to Hep3B cell to construct the recombinant,carrying mda-7/IL-24 gene, by intracellular homologous recombinant. The genomes were analyzed to confirm the recombinant structure.After transfection,choosed 10 recombinant clones,picked out XbaI and XhoI sites,after excise with XbaI and XhoI enzyme, 680 bp and 55 kb slices were positive clones,others were negative clones.
Figure 1 Recombined plasmid pcDNA 3.1-mda-7 identification
M1: λDNA/Hind Ⅲ marker;M2:marker 2000; 1:after excise with enzyme pcDNA3.1/mda-7 showed two positive clones 0.68 and 5.7kb；2：pcDNA 3.1 with unoccupied vector
Expression of mRNA of mda-7/IL-24 Gene
pcDNA 3.1 vector and the recombinant of pcDNA 3.1-mda-7/IL-24 were directionally transfected intoHep3B cell by Lipofectamin. G418 was used to screen the transformants. Total RNA was isolated by Trizol Reagent. Assayed the expression of mRNA of mda-7/IL-24gene with RT-PCR.The result showed that there was a ribbon of 680 bp in mda-7/IL-24 clone but not in pcDNA 3.1 with unoccupied vector and Hep3B cell without transfection.
Figure 2 Expression of mRNA of Mda-7/IL-24 gene in Hep3B cell
M：Marker;1: positive control;2： Hep3B cell with transfection of mda-7/IL-24gene;3:Hep3B cell with transfection of pcDNA 3.1;4：Hep3B cell without transfection
Expression of mda-7/IL-24 Gene in Immunohistochemical Assay
Figure 3 Expression of mda-7 of Hep3B cell without transfection
Figure 4 Expression of mda-7 of Hep3B cell with transfection of pcDNA 3.1
Figure 5 Expression of ,mda-7/IL-24 gene Mda-7/IL-24 Gene affect Hep3B Cell Growth
Figure 6 Mda-7/IL-24 gene affect Hep3B cell growth
After transfection, pcDNA3.1 with unoccupied vector slightly,affect Hep3B cell growth but after transfection of pcDNA 3.1/mda-7/IL-24, Hep3B cell growth slowed down.
Mda-7/IL-24 gene affect Hep3B cell growth, Hep3B cell with transfection of mda-7/IL-24 gene，grew slower than which with pcDNA3.1 with unoccupied vector.
DISCUSSION
Hepatocellular carcinoma were one of the most common incident cancer in China,especially in our city.At present,there was no better method than surgical excision and chemo- and radio-therapy. In the future,a new therapeutic strategy incorporating clinical evidence, molecular biology, and organ replacement needs to be established for the treatment of liver cancer. [4]. Melanoma differentiation-associated gene-7 (mda-7/IL-24 was identified by a combination of recombinant fibroblast interferon (IFN-b) and the protein kinase C activator mezerein (MEZ) subtraction hybridization by Fisher in 1995[5,6]. Mda-7/IL-24,resulted in growth suppression and apoptosis in a broad-spectrum of cancer cell types,in contrast,mda-7/IL-24 does not elicit deleterious effects in normal cells. [7,8]. Wang CJ, et al.confirmed selectively induction of apoptosis and growth suppression by the mda-7/IL-24 gene with replication-incompetent adenovirus vector in human hepatocellular carcinoma cell line HepG2[12].We constructed the mammalian expression recombination pcDNA 3.1-mda-7/IL-24. pcDNA 3.1-mda-7/IL-24 and pcDNA 3.1 was transfected into Hep3B cell respectively. G418 was used to screen the transformants. The expression of mda -7 gene and protein were detected by RT-PCR and immunohistochemistry.We succeed in transfecting pcDNA 3.1-mda-7/IL-24 into Hep3B cell and constructed the liver cancer cell line with highly expression of mda-7/IL-24. According to growth curves,we could see after transfection of pcDNA 3.1/mda-7/IL-24, Hep3B cell growth slowed down and Hep3B cell was inhibited. It was concluded that mda-7/IL-24 gene can inhibit the growth rate of hepatocellular carcinoma cells and as a good candidate of tumor suppressor gene. It has a wide appliable prospect.Our test would play a significant role in researching the mechanism of the apoptosis of liver cancer with transfected mda-7/IL-24.Our test would also offer test data for mda-7/IL-24 gene therapy.
Funding: Nantong Science and Technology Administration (No. S2019)
REFERENCES
1. Sauane M, Gopalkrishnan RV et al. Mda-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev,2003,14(1):35-51.
2. Madireddi MT, Su ZZ et al.Mda-7, a novel melanoma differentiation associated gene with promise for cancer gene therapy. Adv Exp Med Biol, 2000,465:239-61.
3. Jiang H, Su ZZ,et al. The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. Proc Natl Acad Sci U S A, 1996, 93(17):9160-5.
4. Kamohara Y, Kanematsu T.Treatment of liver cancer: current status and future prospectives.Gan To Kagaku Ryoho,2000,27(7):987-992.
5. Lebedeva IV, Su ZZ et al.The cancer growth suppressing gene mda-7 induces apoptosis selectively in human melanoma cells.Oncogene, 2002,21(5):708-18.
6. Su ZZ, Lebedeva IV et al. Melanoma differentiation associated gene-7, mda-7/IL-24, selectively induces growth suppression, apoptosis and radiosensitization in malignant liomas in a p53-independent manner. Oncogene, 2003,22(8):1164-80.
7. Caudell EG, Mumm JB et al.The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol, 2002, 168(12):6041-6.
8. Mhashilkar AM, Schrock RD et al.Melanoma differentiation associated gene-7 (mda-7): a novel anti-tumor gene for cancer gene therapy. Mol Med, 2001,7(4):271-82.
9. Chada S, Sutton RB, Ekmekcioglu S, Ellerhorst J, Mumm JB, Leitner WW, Yang HY, Sahin AA, Hunt KK, Fuson KL, Poindexter N, Roth JA, Ramesh R, Grimm EA, Mhashilkar AM. DA-7/IL-24 is a unique cytokine--tumor suppressor in the IL-10 family. Int Immunopharmacol, 2004,4(5):649-67.
10. Mingzhong Zheng, Dora Bocangel, Blair Doneske, Abner Mhashilkar, Rajagopal Ramesh, Kelly K. Hunt, Suhendan Ekmekcioglu, R. Bryan Sutton, Nancy Poindexter, Elizabeth A. Grimm and Sunil Chada. Human interleukin 24 (MDA-7/IL-24) protein kills breast cancer cells via the IL-20 receptor and is antagonized by IL-10. Cancer Immunol Immunother,2006,19,[Epub ahead of print].
11. Ishikawa S, Nakagawa T, Miyahara R, Kawano Y, Takenaka K, Yanagihara K, Otake Y, Katakura H, Wada H, Tanaka F. Expression of MDA-7/IL-24 and its clinical significance in resected non-small cell lung cancer. Clinical Cancer Research, 2005,11:1198-1202.
12. Wang CJ, Xue XB, Yi JL, Chen K, Zheng JW, Wang J, Zeng JP, Xu RH. Melanoma differentiation-associated gene-7, MDA-7/IL-24, selectively induces growth suppression, apoptosis in human hepatocellular carcinoma cell line HepG2 by replication-incompetent adenovirus vector. World J Gastroenterol, 2006,12(11):1774-9.
(Editor Jaque)(ZHANG Yi-xin1，HUANG Jian-)