Int J Biol Sci 2021; 17(13):3608-3621. doi:10.7150/ijbs.64003 This issue

Research Paper

CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway

Shuai Zhao1,2*, Yichi Zhang1,2*, Xiuqin Lu3*, Han Ding1,2, Bing Han1,2, Xiaoling Song2, Huijie Miao2, Xuya Cui2, Shiyin Wei5✉, Wangrui Liu2,5✉, Shuxian Chen4✉, Jian Wang1,2✉

1. Department of Transplantation, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
3. Shanghai University of Medicine & Health Sciences, Shanghai, P.R. China.
4. Department of Oncology, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5. Department of Neurosurgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi, 533000, China.
*These authors contributed equally to this work.

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Citation:
Zhao S, Zhang Y, Lu X, Ding H, Han B, Song X, Miao H, Cui X, Wei S, Liu W, Chen S, Wang J. CDC20 regulates the cell proliferation and radiosensitivity of P53 mutant HCC cells through the Bcl-2/Bax pathway. Int J Biol Sci 2021; 17(13):3608-3621. doi:10.7150/ijbs.64003. Available from https://www.ijbs.com/v17p3608.htm

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Abstract

Graphic abstract

Purpose: The incidence of hepatocellular carcinoma (HCC) is extremely high, and China accounts for approximately 50% of global liver cancer cases. Previous studies reported that CDC20 is involved in the occurrence and progression of a variety of malignant tumors. So, whether CDC20 will affect the development of HCC, we have conducted in-depth research on this.

Methods: We selected Hep3B and HepG2 for cell culture, and performed siRNA transfection, lentiviral infection, western blot, MTS determination, cell cycle determination, apoptosis test, immunodeficiency test, clone survival test and subcutaneous parthenogenesis in nude mice.

Results: Knockdown of CDC20 greatly enhanced the radiation efficacy on the growth retardation in HepG2, and protein level of CDC20 was decreased for the activation of P53 by radiation. Downregulation of CDC20 combined with radiation can inhibit proliferation, aggravate DNA damage, increase G2/M arrest, and promote apoptosis of HCC cells to a greater extent, and the relative survival fraction of HCC cells was gradually reduced with radiation dose increased in P53 mutated Hep3B cells. After knocking down CDC20 in HCC, Bcl-2 was down-regulated and Bax expression increased. Down-regulation of CDC20 can inhibit further invasion by promoting the radiosensitivity of HCC.

Conclusion: In this study, we found that that CDC20 was highly expressed in HCC and participated in radio resistance of HCC cells with P53 mutation Bcl-2/Bax via signaling pathway. This study is the first to present evidence that CDC20 may play a role in improving the efficacy of radiotherapy in HCC.

Keywords: CDC20, P53 mutant, hepatocellular carcinoma, Bcl-2/Bax pathway