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Effect of combined treatment with lobaplatin and osthole on inducing apoptosis and inhibiting proliferation in human breast cancer MDA-MB-231 cells

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Abstract

The present study investigates the underlying mechanisms of treatment with osthole (OST) combined with lobaplatin in human triple-negative MDA-MB-231 breast cancer cells. Human triple-negative MDA-MB-231 breast cancer cells were treated with different concentrations of OST (0.1, 1, 5, 10, 20, 50, and 100 μM) alone or in combination with 10 μM lobaplatin for 48 h. Cell viability was determined and compared between the treatment groups with the Cell Counting Kit-8 assay. Transcriptome sequencing (Project Number: M-GSGC0250521) was employed to elucidate the gene expression profile of the control group and the OST treatment group, and differentially expressed genes (DEGs) were identified based on the following criteria: log2FC > 0, P < 0.05. KEGG enrichment analysis was employed to determine the biological functions of these DEGs and the related signaling pathways. Finally, flow cytometry and western blotting were used to assess differences in the apoptosis rate and protein expression in MDA-MB-231 cells subjected to different treatments. The findings showed that OST inhibited the growth of MDA-MB-231 cells in a concentration-dependent manner and cell proliferation was significantly inhibited (as indicated by a decrease of 40%) at the OST concentration of 50 μM (P < 0.05). Transcriptome sequencing identified 4712 DEGs, including 2169 upregulated DEGs and 2543 downregulated DEGs. Enrichment analysis indicated that the DEGs played a role in apoptosis, p53 signaling, DNA replication, and cell cycle. In vitro experiments showed that OST and lobaplatin could significantly induce apoptosis in the MDA-MB-231 cells (P < 0.05), as indicated by elevation in the translation level of p53/Bax/caspase-3 p17 and downregulation of the Bcl-2 protein. Finally, combined treatment with OST and lobaplatin had an enhanced anti-tumor effect (P < 0.05) on proliferation and apoptosis, as well as more obvious effects on the related proteins (p53, Bax, Bcl-2, and caspase-3 p17). Thus, OST enhanced the apoptosis-mediated growth inhibitory effect of lobaplatin on breast cancer cells and has potential for the treatment of breast cancer in the future.

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Acknowledgements

All the authors are very grateful to Prof. Xiaowei Qi for providing assistance in reviewing the manuscript.

Funding

This study was supported by the Program for Xinglin Scholars Scientific Research Promotion Plan of Chengdu University of Traditional Chinese Medicine (Grant Number: YYZX20180036) and Project of Young and Middle-aged Innovative Talents of 2017 Jiangbei District.

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Authors and Affiliations

  1. College of Traditional Chinese Medicine, Chongqing Medical University, #1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, People’s Republic of China

    Nan Liu & Shumei Wang

  2. Department of Hematology and Oncology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of China

    Nan Liu & Guoduo Zhang

  3. Department of Breast and Thyroid Surgery, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China

    Hao Tian & Na Sun

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  1. Nan Liu
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  2. Hao Tian
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  4. Na Sun
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  5. Shumei Wang
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Contributions

NL performed the experiment and wrote the paper. NL, HT, MH, and NS contributed to the bioinformatics analysis and figure preparation. HT modified the structure and language of the manuscript. SMW contributed to the conception and design of the study and the revision of the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Shumei Wang.

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Liu, N., Tian, H., Zhang, G. et al. Effect of combined treatment with lobaplatin and osthole on inducing apoptosis and inhibiting proliferation in human breast cancer MDA-MB-231 cells. Med Oncol 39, 16 (2022). https://doi.org/10.1007/s12032-021-01609-4

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