Rapalink-1 and Hydroxychloroquine Exhibit an Additive Effect in Undifferentiated Pleomorphic Sarcoma by Inducing Apoptosis

Abstract

Background/aim: Advanced undifferentiated pleomorphic sarcoma (UPS) has a poor prognosis and there are few treatments that can improve overall survival. Recently, Rapalink-1, a third-generation mammalian target of rapamycin (mTOR) kinase inhibitor, has been developed and shown to be effective against other tumours. However, mTOR inhibitors have been shown to induce autophagy and resistance to anti-cancer drugs. This study aimed to investigate the antitumor effects of Rapalink-1 with an autophagy inhibitor.

Materials and methods: The antitumor effect of Rapalink-1 and/or hydroxychloroquine in three UPS cell lines was examined via cell viability analysis, western blotting, flow cytometry and immunofluorescence.

Results: Rapalink-1 decreased cell proliferation and inhibited the PI3K/mTOR pathway. Combined treatment with Rapalink-1 and hydroxychloroquine enhanced the antitumor effect compared to treatment with Rapalink-1 alone by blocking the autophagy-inducing effect of mTOR inhibitors.

Conclusion: Combined treatment with Rapalink-1 and hydroxychloroquine may be used as a potential therapeutic agent against UPS.

Keywords: Rapalink-1; apoptosis; autophagy; hydroxychloroquine; undifferentiated pleomorphic sarcoma.