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Backgrounds and Purpose: Rapamycin,an mTORC1 allosteric inhibitor with broad antitumor effects,could induce the activation of numerous negative feedback loops such as PI3K/Akt/mTOR signaling pathway,which attenuates its therapeutic efficacy on tumors.OP16 is a novel derivative of oridonin synthesized by our group.In this study,the antitumor effects and the molecular mechanisms of OP16 alone or combined with rapamycin were evaluated in esophageal squamous cell carcinoma(ESCC).