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Overexpression of SIRT3 Inhibits Human Hepatocellular Carcinoma Growth in Ectopic Xenograft Nude Mouse Model and Its Mechanism
Chen Xiang, Ren Jihua, Ran Longkuan, Tao Nana, Li Wanyu, Zhou Hongzhong, Liu Bo, Chen Juan*
Key Laboratory of Molecular Biology on Infection Diseases of Ministry of Education, Chongqing Medical University, Chongqing 400016, China
Abstract: This study investigated the effect of silent information regulator 3 (SIRT3) on the growth of HCC in ectopic xenograft nude mouse model and its possible molecular mechanism. SK-Hep-1 cells were established with stable overexpression of SIRT3 or pcDNA3.1， respectively. Then， these cells were injected to the subcutaneous of nude mice， respectively. The growth of ectopic xenograft in SIRT3 group and pcDNA3.1 group were monitored at regular intervals. The ectopic xenograft were stripped out and weighed at 25th day after injection. Expression levels of SIRT3 and Ki-67 were determined by immunohistochemical staining. Downstream target molecules， which may participate in the SIRT3 pathway that regulated the growth of transplantation tumor， were analyzed by reverse-transcription polymerase chain reaction (qRT-PCR). Bax and cleaved-PARP were detected by Western blot. The results showed that SIRT3 overexpression could decrease the size and weight of ectopic xenograft and downregulate the expression of Ki-67. Furthermore， overexpression of SIRT3 raised the Bax in mRNA and protein levels， and promoted the protein cleavage of PARP. These results demonstrated that SIRT3 might inhibit the growth of human HCC ectopic xenograft by Bax signaling pathway in apoptosis.
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