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Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability

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Abstract

Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.

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Acknowledgements

We acknowledge Dr. Hui Wang from Pub-Lab Platform, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, for assistance with the flow cytometry (BD, FACS Melody) and fluorescence microscope (Zeiss, AxioObserver7).

Funding

This research was funded by the Undergraduate Innovation and Entrepreneurship Training Program of Sichuan University.

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  1. Peipei Wang and Shitong Min contributed equally to this study.

Authors and Affiliations

  1. West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, China

    Peipei Wang, Shitong Min, Congliang Chen, Junmei Hu, Dapeng Wei & Xia Wang

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Contributions

PPW, and XW designed the experiments. PPW, STM, JMH, CLC and DPW performed the experiments and collected the data. STM supervised the experiments, interpreted the data and wrote the article. PPW supervised and complemented the writing. All authors have read and approved the manuscript.

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Correspondence to Xia Wang.

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Wang, P., Min, S., Chen, C. et al. Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability. J Nat Med 78, 355–369 (2024). https://doi.org/10.1007/s11418-023-01772-0

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