Int J Biol Sci 2022; 18(14):5221-5229. doi:10.7150/ijbs.67869 This issue

Research Paper

MG53 inhibits cellular proliferation and tumor progression in colorectal carcinoma

Pranav Gupta1#*, Haichang Li2✉*, Guan-Nan Zhang1, Anna Maria Barbuti1, Yuqi Yang1, Pei-hui Lin2, Chuanxi Cai2, Tao Tan2, Jianjie Ma2, Zhe-Sheng Chen1✉

1. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
2. Department of Surgery, The Ohio State University, Columbus, OH 43210, USA.
# Current affiliation: Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA.
* These authors contributed equally.

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Citation:
Gupta P, Li H, Zhang GN, Barbuti AM, Yang Y, Lin Ph, Cai C, Tan T, Ma J, Chen ZS. MG53 inhibits cellular proliferation and tumor progression in colorectal carcinoma. Int J Biol Sci 2022; 18(14):5221-5229. doi:10.7150/ijbs.67869. Available from https://www.ijbs.com/v18p5221.htm

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Abstract

Graphic abstract

Cancer is the second leading cause of mortality after cardiovascular diseases in the United States. Chemotherapy is widely used to treat cancers. Since the development of drug resistance is a major contributor towards the failure of chemotherapeutic regimens, efforts have been made to develop novel inhibitors that can combat drug resistance and sensitize cancer cells to chemotherapy. Here we investigated the anti-cancer effects of MG53, a TRIM-family protein known for its membrane repair functions. We found that rhMG53 reduced cellular proliferation of both parental and ABCB1 overexpressing colorectal carcinoma cells. Exogenous rhMG53 protein entered SW620 and SW620/AD300 cells without altering the expression of ABCB1 protein. In a mouse SW620/AD300 xenograft model, the combination of rhMG53 and doxorubicin treatment significantly inhibited tumor growth without any apparent weight loss or hematological toxicity in the animals. Our data show that MG53 has anti-proliferative function on colorectal carcinoma, regardless of their nature to drug-resistance. This is important as it supports the broader value for rhMG53 as a potential adjuvant therapeutic to treat cancers even when drug-resistance develops.

Keywords: Cancer, Drug Resistance, ABCB1, rhMG53, Doxorubicin