Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Ma,Lu; Li,Xin; Zhao,Xiaopeng; Sun,Haotong; Kong,Feifei; Li,Yuanjie; Sui,Yu; Xu,Fang

doi:10.3892/mmr.2021.12268

Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells

Authors:
- Lu Ma
- Xin Li
- Xiaopeng Zhao
- Haotong Sun
- Feifei Kong
- Yuanjie Li
- Yu Sui
- Fang Xu
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Affiliations: Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Oncology, Qufu People's Hospital, Qufu, Shandong 273100, P.R. China
Published online on: July 5, 2021 https://doi.org/10.3892/mmr.2021.12268
Article Number: 629
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The clinical efficacy of colorectal tumor treatment is restricted due to platinum agent resistance. Translesion DNA synthesis (TLS) has been shown to contribute to this resistance; however, the exact molecular mechanism remains unknown. The present study aimed to investigate the possible function of the core of the TLS polymerase mitotic arrest deficient 2 like 2 (MAD2L2) in drug sensitivity, in order to provide a treatment rationale for platinum‑based chemotherapy in colon cancer. In the present study, MAD2L2 was knocked down using MAD2L2‑specific small interfering (si)RNA. HCT116 and SW620 cells were treated with oxaliplatin and MG132; oxaliplatin is a platinum compound that induces DNA damage and MG132 is a potent proteasome inhibitor. Cell viability was determined using an MTT assay. Cell apoptosis was examined via flow cytometry and TUNEL assay. The activity of proteasome 26S subunit, non‑ATPase 13 (PSMD13) was detected using ELISA, while the expression levels of apoptotic‑related proteins were detected via western blotting. The results demonstrated that cells treated with oxaliplatin or MG132 alone had decreased viability, but a synergistic effect was not observed after co‑treatment. In addition, the knockdown of MAD2L2 caused by siMAD2L2 or oxaliplatin treatment increased the expression levels of the pro‑apoptotic proteins Bax and Bak and decreased the expression levels of the anti‑apoptotic protein Bcl‑2, compared with the negative control group. Moreover, MG132 alleviated the decrease in MAD2L2 expression, while reducing siMAD2L2‑induced cell apoptosis. These results indicate that oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells. This process was associated with the Bcl‑2 and ubiquitin‑proteasome pathway. Overall, the present study provides a theoretical basis for improving the clinical efficacy of colon cancer by combining chemotherapy and gene therapy.

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