ARL6IP1 mediates cisplatin-induced apoptosis in CaSki cervical cancer cells.
Cisplatin has been shown to induce apoptosis in various types of cancer cells. Despite the great efficacy at treating certain kinds of cancers, cisplatin introduced into clinical use shows side effects and the acquisition or presence of resistance to the drug. Thus, it is important that we further understand the anti-cancer mechanism of cisplatin with the goal of enhancing its efficacy. ADP-ribosylation factor-like 6 interacting protein 1 (ARL6IP1) is an apoptotic regulator. We studied cisplatin-induced apoptosis with suppression of ARL6IP1 expression in CaSki cervical cancer cells. Exogenous expression of ARL6IP1 suppressed cisplatin-induced apoptosis in CaSki cells, and siRNA-induced silencing of ARL6IP1 triggered apoptosis in CaSki cells even in the absence of other apoptotic stimuli. Cisplatin treatment induced caspase-3, -9, p53, Bax, NF-kappaB and MAPK expression, and suppressed Bcl-2 and Bcl-xl expression, whereas cells transfected with pcDNA3.1-ARL6IP1 showed lower levels of cisplatin-induced caspase-3, -9, p53, Bax, NF-kappaB and MAPK up-regulation and higher levels of cisplatin-suppressed Bcl-2 and Bcl-xl down-regulation. These novel findings collectively suggest that ARL6IP1 may play a key role in cisplatin-induced apoptosis in CaSki cervical cancer cells by regulating the expression of apoptosis-associated proteins such as caspase-3, -9, p53, NF-kappaB, MAPK, Bcl-2, Bcl-xl, and Bax.
Guo
Fengjie
F
Cancer Research Institute, Xiangya Medical School, Central South University, Changsha 410078, P.R. China.
Li
Yalin
Y
Liu
Yan
Y
Wang
Jiajia
J
Li
Guancheng
G
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
C488848:ARL6IP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008565:Membrane Proteins; D002945:Cisplatin