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Study of Synergistic Suppression on Hep3B Cells by Combining ZD55-IL24 with Rapamycin
Zhuo Lingyan, Ma Buyun, Huang Panpan, Zhang Rong, Jia Xiaoyuan, Zhou Xiumei, Wang Yigang*
Xin Yuan Institute of Medicine and Biotechnology College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China
Abstract: Activation of PI3K/AKT/mTOR signal pathway can trigger the formation of human solid tumors. mTOR， as a downstream effector of the PI3K/AKT pathway， is a key therapeutic target involved in oncogenesis and progression of cancer. Therefore， blocking relevant targets of this pathway could be a novel treatment strategy for human malignancies. IL24 (interleukin 24)， which is able to selectively induce tumor cell apoptosis， is an important antitumor gene. In this study， we explored the killing effects of either oncolytic adenovirus mediated IL24 gene (ZD55-IL24) alone or in combination with novel immunosuppressor， rapamycin， against hepatoma cells in vitro by MTT detecting method and the iCELLigence real time cellular analysis system. The morphological analysis was assessed by inverted microscope in hepatoma cells treated by single ZD55-IL24 or rapamycin， and their combination. Hoechst 33342 staining， flow cytometry assay and TUNEL were performed to determine the apoptosis effects of single and combinational therapy on hepatoma cells， respectively. The protein levels of IL24， AKT， and apoptosis related protein Bax and Bcl-2 were determined by Western blot. The results indicated that the combination treatment of oncolytic adenovirus ZD55-IL24 and rapamycin remarkably inhibited Hep3B cell proliferation and induced the cell apoptosis compared with ZD55-IL24 alone or rapamycin alone. Furthermore， the combination
treatment significantly up-regulated cytokines IL24 and apoptosis-induction protein Bax expression， while downregulated the key protein AKT expression of PI3K/AKT/ mTOR signal pathway and anti-apoptosis protein Bcl-2 expression. In conclusion， the results showed that rapamycin could promote the expression mediated by ZD55-IL24 replication and strengthen its antitumor effects in hepatoma cells in vitro， which provides a novel and promising therapeutic approach for targeting treatment of hepatoma cells.
treatment significantly up-regulated cytokines IL24 and apoptosis-induction protein Bax expression， while downregulated the key protein AKT expression of PI3K/AKT/ mTOR signal pathway and anti-apoptosis protein Bcl-2 expression. In conclusion， the results showed that rapamycin could promote the expression mediated by ZD55-IL24 replication and strengthen its antitumor effects in hepatoma cells in vitro， which provides a novel and promising therapeutic approach for targeting treatment of hepatoma cells.
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