title: Cucurbitacin E inhibits osteosarcoma cells proliferation and invasion through attenuation of PI3K/AKT/mTOR signalling pathway.
abstract: Cucurbitacin E (CuE), a potent member of triterpenoid family isolated from plants, has been confirmed as an antitumour agent by inhibiting proliferation, migration and metastasis in diverse cancer. However, the effects and mechanisms of CuE on osteosarcoma (OS) have not been well understood. The present study aimed to test whether CuE could inhibit growth and invasion of OS cells and reveal its underlying molecular mechanism. After various concentrations of CuE treatment, the anti-proliferative effect of CuE was assessed using the cell counting Kit-8 assay. Flow cytometry analysis was employed to measure apoptosis of OS cells. Cell cycle distribution was analysed by propidium iodide staining. Transwell assay was performed to evaluate the effect of CuE on invasion potential of OS cells. The protein levels were measured by western blot. In addition, the potency of CuE on OS cells growth inhibition was assessedin vivoOur results showed that CuE inhibited cell growth and invasion, induced a cell cycle arrest and triggered apoptosis and modulated the expression of cell growth, cell cycle and cell apoptosis regulators. Moreover, CuE inhibited the PI3K/Akt/mTOR pathway and epithelial-mesenchymal transition (EMT), which suppressed the invasion and metastasis of OS. In addition, we also found that CuE inhibited OS cell growthin vivoTaken together, our study demonstrated that CuE could inhibit OS tumour growth and invasion through inhibiting the PI3K/Akt/mTOR signalling pathway. Our findings suggest that CuE can be considered to be a promising anti-cancer agent for OS.
authors.affiliation: Department of Acupuncture, Tuina and Traumatology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Lanzhou General Hospital, Lanzhou Command of CPLA, Lanzhou 730050, China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Acupuncture, Tuina and Traumatology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China wu_yaochi@126.com.
authors.forename: Yaochi
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Acupuncture, Tuina and Traumatology, the Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200233, China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
keywords: Akt; PI3K; apoptosis; cell cycle; cucurbitacin E; mTOR signalling; osteosarcoma; proliferation