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Rapamycin inhibits B16 melanoma cell viability in vitro and in vivo by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway

  • Authors:
    • Penghui Wang
    • Haifang Zhang
    • Kaikai Guo
    • Chun Liu
    • Shimin Chen
    • Baopeng Pu
    • Sirun Chen
    • Tong Feng
    • Hanyi Jiao
    • Chang Gao
  • View Affiliations / Copyright

    Affiliations: Department of Basic Medicine and Life Sciences, Hainan Medical University, Haikou, Hainan 570100, P.R. China, Hainan Institute for Drug Control, Haikou, Hainan 570216, P.R. China, Hainan Medical University Press, Hainan Medical University, Haikou, Hainan 570100, P.R. China, School of Pharmacy, Hainan Medical University, Haikou, Hainan 570100, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 140
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    Published online on: February 2, 2024
       https://doi.org/10.3892/ol.2024.14273
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Abstract

Rapamycin is an immunosuppressant that has been shown to prevent tumor growth following organ transplantation. However, its exact mode of antitumor action remains unknown. The present study used the B16‑F10 (B16) murine melanoma model to explore the antitumor mechanism of rapamycin, and it was revealed that rapamycin reduced B16 cell viability in vitro and in vivo. In addition, in vitro and in vivo, the results of western blotting showed that rapamycin reduced Bcl2 expression, and enhanced the protein expression levels of cleaved caspase 3 and Bax, indicating that it can induce the apoptosis of B16 melanoma cells. Furthermore, the results of cell cycle analysis and western blotting showed that rapamycin induced B16 cell cycle arrest in the G1 phase, based on the reduction in the protein expression levels of CDK1, cyclin D1 and CDK4, as well as the increase in the percentage of cells in G1 phase. Rapamycin also significantly increased the number of autophagosomes in B16 melanoma cells, as determined by transmission electron microscopy. Furthermore, the results of RT‑qPCR and western blotting showed that rapamycin upregulated the protein expression levels of microtubule‑associated protein light chain 3 (LC3) and Beclin‑1, while downregulating the expression of p62 in vitro and in vivo, thus indicating that rapamycin could trigger cellular autophagy. The present study revealed that rapamycin in combination with chloroquine (CQ) further increased LC3 expression compared with that in the CQ group, suggesting that rapamycin induced an increase in autophagy in B16 cells. Furthermore, the results of western blotting showed that rapamycin blocked the phosphorylation of p70 ribosomal S6 kinase (p70‑S6k) and mammalian target of rapamycin (mTOR) proteins in vitro and in vivo, thus suggesting that rapamycin may exert its antitumor effect by inhibiting the phosphorylation of the mTOR/p70‑S6k pathway. In conclusion, rapamycin may inhibit tumor growth by inducing cellular G1 phase arrest and apoptosis. In addition, rapamycin may exert its antitumor effects by inducing the autophagy of B16 melanoma cells in vitro and in vivo, and the mTOR/p70‑S6k signaling pathway may be involved in this process.
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Copy and paste a formatted citation
Spandidos Publications style
Wang P, Zhang H, Guo K, Liu C, Chen S, Pu B, Chen S, Feng T, Jiao H, Gao C, Gao C, et al: Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway. Oncol Lett 27: 140, 2024.
APA
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B. ... Gao, C. (2024). Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway. Oncology Letters, 27, 140. https://doi.org/10.3892/ol.2024.14273
MLA
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B., Chen, S., Feng, T., Jiao, H., Gao, C."Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway". Oncology Letters 27.4 (2024): 140.
Chicago
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B., Chen, S., Feng, T., Jiao, H., Gao, C."Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway". Oncology Letters 27, no. 4 (2024): 140. https://doi.org/10.3892/ol.2024.14273
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x
Spandidos Publications style
Wang P, Zhang H, Guo K, Liu C, Chen S, Pu B, Chen S, Feng T, Jiao H, Gao C, Gao C, et al: Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway. Oncol Lett 27: 140, 2024.
APA
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B. ... Gao, C. (2024). Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway. Oncology Letters, 27, 140. https://doi.org/10.3892/ol.2024.14273
MLA
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B., Chen, S., Feng, T., Jiao, H., Gao, C."Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway". Oncology Letters 27.4 (2024): 140.
Chicago
Wang, P., Zhang, H., Guo, K., Liu, C., Chen, S., Pu, B., Chen, S., Feng, T., Jiao, H., Gao, C."Rapamycin inhibits B16 melanoma cell viability <em>in</em> <em>vitro</em> and <em>in</em> <em>vivo</em> by inducing autophagy and inhibiting the mTOR/p70‑S6k pathway". Oncology Letters 27, no. 4 (2024): 140. https://doi.org/10.3892/ol.2024.14273
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