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The inhibitory effects of deleted in liver cancer 1 gene on gallbladder cancer growth through induction of cell cycle arrest and apoptosis
Author(s) -
Qin Yiyu,
Chu Bingfeng,
Gong Wei,
Wang Jiandong,
Tang Zhaohui,
Shen Jun,
Quan Zhiwei
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12486
Subject(s) - ectopic expression , apoptosis , cell cycle , cell growth , cell cycle checkpoint , gallbladder cancer , cancer research , biology , in vivo , cell , microbiology and biotechnology , cell culture , cancer , biochemistry , genetics
Background and Aim The biological function of tumor suppressor deleted in liver cancer 1 ( DLC 1) has been investigated in several types of human cancer, but its role in gallbladder cancer ( GBC ) is yet to be determined. In this research, we conducted in vitro and in vivo analysis to evaluate the inhibitory activities of DLC 1 gene against GBC growth. Methods DLC 1 expression in GBC tissues and cell lines was examined by immunohistochemical staining, reverse transcription polymerase chain reaction, and Western blot assay. The in vitro and in vivo effects of ectopic DLC 1 expression on cell growth were evaluated. In addition, the effects of ectopic DLC 1 expression on cell cycle, apoptosis, and migration were also evaluated. The expressions of cell cycle‐related and apoptosis‐related proteins were examined. Results The downregulation of DLC 1 expression was a common event in GBC tissues and cell lines. Restoration of DLC 1 expression in GBC‐SD and NOZ cells significantly reduced cell proliferation, migration in vitro, and the ability of these cells to form tumors in vivo. Restoration of DLC 1 expression arrested GBC‐SD and NOZ cells in G 0/ G 1 phase through inducing p21 in a p53‐independent manner. In addition, restoration of DLC 1 expression induced extrinsic and intrinsic apoptotic pathway through promoting the expressions of F as L / FADD , Bax, cytochrome c, cleaved caspase‐8, ‐9, ‐3, and cleaved poly‐(ADP‐ribose) polymerase and suppressing bcl‐2 expression in GBC‐SD and NOZ cells. Conclusions Our findings suggested that dysregulated expression of DLC 1 is involved in proliferation and invasion of GBC cells and may serve as a potential therapeutic target.