The co-transfection of p16(INK4a) and p14(ARF) genes into human lung cancer cell line A549 and the effects on cell growth and chemosensitivity.
Two functionally and structurally different proteins, p16(INK4a) and p14(ARF), encoded by the gene INK4a/ARF located at 9p21 are cyclin-dependent kinase (cdk) inhibitors and important cell cycle regulators. More and more evidences have been accumulated to show that the exogenous p16(INK4a) or p14(ARF) can inhibit the cell growth and/or induce the apoptosis. But it is still unclear if they can play positive role when combine with the conventional chemotherapy in cancer treatment. Here we show that cationic liposome-mediated gene transfection of INK4a/ARF into lung cancer cell line A549, in which the INK4a/ARF locus was lost, suppressed the growth and induced apoptosis. When treated with five different chemotherapy drugs with different mechanism after the transfection, A549 got an increased chemosensitivity for adriamycin and cisplatin and an unchanged result for topotecan, taxol or vinorelbine. The results indicated that cell cycle redistribution and increased apoptosis index after transfection might be the main explanation for the enhanced chemosensitivity. The combination of gene therapy with conventional chemotherapy is not always better than single chemotherapy. This trial will be of benefit to the treatment of lung cancer when combine the conventional chemotherapy and gene therapy in the future.
Xie
Qi-Chao
QC
Cancer Center of Xinqiao Hospital, The Third Military Medical University of PLA, Chongqing 400037, PR China.
Hu
Yi-de
YD
Wang
Ling-Li
LL
Chen
Zheng-Tang
ZT
Diao
Xin-Wei
XW
Wang
Zhi-Xin
ZX
Guan
Hua-Jun
HJ
Zhu
Bo
B
Sun
Jian-Guo
JG
Duan
Yu-Zhong
YZ
Chen
Fang-Lin
FL
Nian
Wei-Qi
WQ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division / Q000235:genetics*; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D010957:Plasmids; D014162:Transfection; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics*
D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF