Silencing Livin induces apoptotic and autophagic cell death, increasing chemotherapeutic sensitivity to cisplatin of renal carcinoma cells.
Renal cell carcinoma (RCC) accounts for 3 % of all adult malignancies and is the most lethal urological cancer. Livin is a member of the inhibitor of apoptosis protein (IAP) family, which is associated with tumor resistance to radiotherapy and chemotherapy. Clinical data also showed that patients with high tumor grades and stages have higher expression levels of Livin in RCC cells. Autophagy is a survival mechanism activated in response to nutrient deprivation. A possible role of Livin in the autophagy of RCC cells has not been investigated; therefore, this pioneer study was carried out. Livin was silenced in RCC cells (slow virus infection [SVI]-shLivin cells) by lentiviral transfection. Then, mRNA and protein expression levels in the transfected cells were assessed by quantitative fluorescence PCR and Western blotting, respectively. In addition, acridine orange staining and electron microscopy were used to assess autophagy in SVI-shLivin cells. The cisplatin IC50 values for RCC cells were measured by the CCK8 assay. Potent antitumor activities were observed in xenograft mouse models generated with Livin-silenced RCC cells in terms of delayed tumor onset and suppressed tumor growth. These results suggested that Livin silencing could increase the chemotherapeutic sensitivity of RCC cells to cisplatin and induce autophagic cell death. A possible mechanism of Bcl-2 and Akt pathway involvement was discussed specifically in this study. Overall, Livin silencing induces apoptotic and autophagic cell death and increases chemotherapeutic sensitivity of RCC cells to cisplatin.
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Zhiyang
Z
Wang
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Shuai
S
Liu
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Kejia
K
Ding
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Sentai
S
Ding
Department of Digestive Diseases, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People's Republic of China.
Chensheng
C
Li
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Jiaju
J
Lu
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Dexuan
D
Gao
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China.
Tong
T
Zhang
Department of Urology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Street, Jinan, 250021, People's Republic of China. dongbinbimedical@126.com.
Dongbin
D
Bi
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C419866:BIRC7 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002945:Cisplatin
Autophagic cell death; Autophagy; Chemotherapeutic sensitivity; Livin; Renal cell carcinoma
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