白藜芦醇对胶质母细胞瘤作用以及与STAT3信号通路的关系研究

The progress of resveratrol effect target on glioblastoma and its related STAT3 cell signaling

白藜芦醇是国际上公认的癌症化学预防剂,具有抑制大量癌细胞增殖并诱导细胞走向凋亡的特点。该化合物具有脂溶性,能够通过血脑屏障达到药物的有效利用度,从而发挥其生物作用,提示白藜芦醇可成为治疗颅内恶性肿瘤的理想药物。原发性脑肿瘤是严重威胁人类健康的常见神经系统肿瘤,其中以好发于成人期的胶质母细胞瘤(Glioblastoma multiform,GBM)威胁最大。该肿瘤具有高侵袭性及扩散性等特点,临床上尚无有效治疗手段。因此,寻求毒副作用低的抗GBM新药并深入分析其作用靶点,具有重要的临床转化意义。近阶段研究发现,JAK-STAT3信号通路在GBM的发生和发展中发挥重要的促进作用,其特异性的STAT3负向调控因子也参与了GBM异常增殖。本文结合国内外最新研究进展,综述了GBM中STAT3信号通路及其负反馈因子的生物学作用,以及STAT3作为白藜芦醇的重要作用靶点,为今后胶质母细胞瘤临床个体化治疗探索新思路,新途径。

Resveratrol is the internationally recognized cancer chemoprevention agent. It could inhibit cancer cell proliferation and induce cells to apoptosis. Because of the liposoluble of resveratrol, it can exert its biological function through the blood-brain barrier in the effective exploitation degree, which prompts resveratrol can be used as an ideal drug for the treatment of intracranial malignant tumor. Primary brain tumor is one of the common nervous system tumors which seriously threaten the health of mankind. And glioblastoma multiform（GBM） occurs in adulthood is the biggest threat. It has the characteristics of high aggressive and invasive tumors, there is no effective treatment clinically. Therefore, seeking the anti-GBM drug with the low toxic and side effects is as significant as analyzing its targets. It has been recognized that activated STAT3 signaling is critical for the growth and survival of glioblastma. It has also been known that three negatively regulators can negatively regulate STAT3 signaling. Nevertheless, the expression statuses, biological functions and relevance with chemosensitivity of these three factors in human primary brain malignancies remain obscure. This paper aims to review the biological effect of JAK-STAT3 cell signaling and it＇s negatively regulators. We also conclude the STAT3 cell signaling as the main target of resvertrol to explore the new way in resveratrol-based personalized therapy for primary brain malignancies.