Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase

Shi, Xiaorui; Li, Hongxia; Dan, Zhangyong; Shu, Chuanlin; Zhu, Rumeng; Yang, Qingling; Wang, Yi; Zhu, Huaqing

doi:10.7150/jca.85353

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J Cancer 2023; 14(14):2608-2618. doi:10.7150/jca.85353 This issue Cite

Research Paper

Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase

Xiaorui Shi^1#, Hongxia Li^3#, Zhangyong Dan^1#, Chuanlin Shu¹, Rumeng Zhu¹, Qingling Yang⁴, Yi Wang^1,2,4✉, Huaqing Zhu^1✉

1. Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei 230032, China.
2. Department of Biological Engineering, School of Life Sciences, Anhui Medical University, Hefei 230032, China.
3. Department of Oncology, The Third Affiliated Hospital of Anhui Medical University, Hefei 230032, China.
4. Anhui Province Key Laboratory of Translational Cancer Research, Bengbu Medical College, Anhui 233030, China.
# These authors contributed equally to this work.

Citation:

Shi X, Li H, Dan Z, Shu C, Zhu R, Yang Q, Wang Y, Zhu H. Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase. J Cancer 2023; 14(14):2608-2618. doi:10.7150/jca.85353. https://www.jcancer.org/v14p2608.htm

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Abstract

5-Fluorouracil is an effective chemotherapeutic drug for gastric cancer. However, the acquisition of chemotherapeutic resistance remains a challenge in treatment. Melatonin can enhance the therapeutic effect of 5-fluorouracil; however, the underlying mechanisms are not well understood. We investigated the effects of combinations of melatonin and 5-fluorouracil on the proliferation, migration and invasion of gastric cancer cells. Melatonin significantly potentiated the 5-fluorouracil-mediated inhibition of proliferation, migration and invasion in gastric cancer cells, which potentiates sensitivity to 5-FU by promoting the activation of Beclin-1-dependent autophagy and targeting the myosin light-chain kinase (MLCK) signaling pathway. Previous studies have shown that autophagy might be associated with the MLCK signaling pathway. The autophagy inhibitor, 3-methyladenine, effectively rescued the migratory and invasive capabilities of gastric cancer cells, while also reducing expression level of MLCK and the phosphorylation level of MLC. This indicates that autophagy is involved in tumor metastasis, which may be related to inhibition of the MLCK signaling pathway. Our findings indicate that melatonin can improve the effectiveness of 5-fluorouracil in gastric cancer and could be used as a supplemental agent in the treatment of gastric cancer with 5-fluorouracil.

Keywords: melatonin, 5-Fluorouracil, autophagy, gastric cancer, MLCK

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APA

Shi, X., Li, H., Dan, Z., Shu, C., Zhu, R., Yang, Q., Wang, Y., Zhu, H. (2023). Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase. Journal of Cancer, 14(14), 2608-2618. https://doi.org/10.7150/jca.85353.

ACS

Shi, X.; Li, H.; Dan, Z.; Shu, C.; Zhu, R.; Yang, Q.; Wang, Y.; Zhu, H. Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase. J. Cancer 2023, 14 (14), 2608-2618. DOI: 10.7150/jca.85353.

NLM

CSE

Shi X, Li H, Dan Z, Shu C, Zhu R, Yang Q, Wang Y, Zhu H. 2023. Melatonin Potentiates Sensitivity to 5-Fluorouracil in Gastric Cancer Cells by Upregulating Autophagy and Downregulating Myosin Light-Chain Kinase. J Cancer. 14(14):2608-2618.

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