The mechanism of treatment of multiple myeloma with metformin by way of metabolism
Yanyan Song 1,   Song Chen 2,   Wei Xiang 1,   Muran Xiao 1,   Hui Xiao 1
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Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan, China
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China
Submission date: 2019-01-05
Final revision date: 2019-03-07
Acceptance date: 2019-03-18
Online publication date: 2020-11-29
Multiple myeloma (MM) is a malignant hematologic tumor. Although many new drugs are currently found to significantly improve the median survival, MM is still not curable due partly to drug resistance recurrence. Epidemiological studies have shown that patients with type 2 diabetes have a high risk of malignancy, and patients’ treatment with metformin could reduce the risk of cancer as well as associated mortality.

Material and methods:
We used chemotherapeutics – melphalan combined with metformin or the single drug – to treat RPMI8226 cells and used a series of tests to detect the drug sensitivity, apoptotic rate, DNA damage and the concentration of ATP. SPSS 17.0 was used to analyze the data.

The inhibitory effect of melphalan on RPMI8226 cells was significantly increased after metformin was added (p < 0.05), and the inhibitory effect was enhanced with the increasing concentration of melphalan. The comet assay showed that metformin increased melphalan-induced DNA damage and increased the apoptotic rate from 12.7 ±2.8% to 18.8 ±1.5% (p < 0.05). In the ATP concentration test, the concentration of ATP in the tumor cells was significantly decreased from 0.42 ±0.01 µmol/l to 0.08 ±0.02 µmol/l (p < 0.05).

Metformin can promote DNA damage induced by melphalan and decrease the concentration of ATP in the process of repairing DNA damage to hinder the anti-apoptotic process of tumor cells, which showed the pesticide effect of the enhanced sensitivity of multiple myeloma cells to melphalan.