Liu Dongjie, Liu Mingyang, Wang Wenjing, Pang Lijun, Wang Zhenchang, Yuan Chunwang, Liu Kai
Beijing Institute of Hepatology, Beijing, 100069, China; Capital Medical University Affiliated Beijing You an Hospital, Beijing, 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, 100069, China; Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014040, China.
General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin 150088, China.
Biochem Biophys Res Commun. 2018 Apr 6;498(3):453-457. doi: 10.1016/j.bbrc.2018.02.203. Epub 2018 Mar 1.
Full-length apoptosis-inducing factor mitochondrion-associated 1 (AIFM1) (∼67 kDa) induces apoptosis in a caspase-independent manner when it is cleaved at its N-terminus to produce truncated AIFM1 (∼57 kDa). Here, we produced recombinant adenovirus AIFM1 (rAd-AIFM1) encoding full-length AIFM1 to detect whether full-length AIFM1 suppresses cell growth and induces apoptosis of hepatoma cell lines (HepG2 and Hep3B). Hepatocellular carcinoma (HCC) is one of the most difficult cancers to treat worldwide. The MTT assay demonstrated that full-length AIFM1 inhibited the growth of hepatoma cells because rAd-AIFM1 infection suppressed the proliferation of HepG2 and Hep3B cells. TUNEL assay demonstrated that full-length AIFM1 overexpression induced apoptosis in HepG2 and Hep3B cells infected with rAd-AIFM1, suggesting an apoptosis-inducing ability of full-length AIFM1. Our data further showed that the expression of two pro-apoptotic genes, caspase3 and DRAM, were involved in full-length AIFM1 infection-induced apoptosis, and full-length AIFM1 could also positively regulate the transcription of caspase3 and DRAM. Thus, overexpression of full-length AIFM1 can induce caspase-dependent apoptosis and suppresses cell growth of hepatoma cells. Our data uncover a potential role of rAd-AIFM1 in HCC gene therapy.
全长凋亡诱导因子线粒体相关蛋白1（AIFM1）（约67 kDa）在其N端被切割产生截短的AIFM1（约57 kDa）时，以不依赖半胱天冬酶的方式诱导细胞凋亡。在此，我们构建了编码全长AIFM1的重组腺病毒AIFM1（rAd-AIFM1），以检测全长AIFM1是否能抑制肝癌细胞系（HepG2和Hep3B）的细胞生长并诱导其凋亡。肝细胞癌（HCC）是全球最难治疗的癌症之一。MTT法表明全长AIFM1抑制肝癌细胞生长，因为rAd-AIFM1感染抑制了HepG2和Hep3B细胞的增殖。TUNEL法表明全长AIFM1过表达可诱导感染rAd-AIFM1的HepG2和Hep3B细胞凋亡，提示全长AIFM1具有诱导凋亡的能力。我们的数据进一步表明，两个促凋亡基因caspase3和DRAM的表达参与了全长AIFM1感染诱导的凋亡，并且全长AIFM1还可以正向调节caspase3和DRAM的转录。因此，全长AIFM1的过表达可诱导依赖半胱天冬酶的凋亡并抑制肝癌细胞的生长。我们的数据揭示了rAd-AIFM1在肝癌基因治疗中的潜在作用。
