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Published on: September 30, 2016
MG53 inhibits cellular proliferation and tumor progression in colorectal carcinoma
Pranav Gupta1, Haichang Li2, Guan-Nan Zhang1
1Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY 11439, USA.
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.
Insights
Recombinant human MG53 (rhMG53) protein inhibits colorectal cancer cell growth, even in drug-resistant cells. Combined with doxorubicin, rhMG53 effectively reduced tumor growth in mice without significant toxicity, showing potential as an adjuvant cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cancer is a leading cause of death, with chemotherapy often failing due to drug resistance.
- Developing novel therapeutic strategies to overcome chemoresistance is crucial for improving patient outcomes.
- MG53, a TRIM-family protein, is known for its role in membrane repair.
Purpose of the Study:
- To investigate the anti-cancer effects of recombinant human MG53 (rhMG53) on colorectal carcinoma cells.
- To determine if rhMG53 can overcome chemoresistance mediated by ABCB1.
- To evaluate the efficacy and safety of rhMG53 in combination with doxorubicin in a preclinical cancer model.
Main Methods:
- Cell proliferation assays were performed on parental and ABCB1-overexpressing colorectal cancer cells treated with rhMG53.
- Cellular uptake of rhMG53 and its effect on ABCB1 expression were analyzed.
- A mouse xenograft model using SW620/AD300 cells was employed to assess the in vivo efficacy of rhMG53 combined with doxorubicin.
Main Results:
- rhMG53 significantly reduced the proliferation of both drug-sensitive and drug-resistant colorectal cancer cells.
- Exogenous rhMG53 entered cancer cells without affecting ABCB1 expression levels.
- Combination therapy with rhMG53 and doxorubicin markedly inhibited tumor growth in mice, with no observed weight loss or hematological toxicity.
Conclusions:
- MG53 exhibits anti-proliferative activity against colorectal carcinoma, irrespective of drug-resistance mechanisms.
- rhMG53 demonstrates potential as an adjuvant therapeutic agent for treating cancers, including those that have developed resistance to conventional chemotherapy.
- These findings support the broader therapeutic value of rhMG53 in oncology.
