Molecular Medicine Institute, Life Science College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Aging (Albany NY). 2021 Nov 5;13(21):24101-24116. doi: 10.18632/aging.203662.
Currently, conventional treatment is not sufficient to improve the survival of glioma patients. Hence, adopting novel personalized treatment programs is imperative. Curcumol, a Chinese herbal medicine extract from the roots of , has attracted significant interest due to its beneficial pharmacological activities. The current study revealed that curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance in glioma cells and . Next, the potential molecular mechanisms of curcumol in inhibiting glioma were investigated. We found that the long non-coding RNA (lncRNA) FOXD2-As1 might contribute to the effects of curcumol on glioma cells. Enforced expression of FOXD2-As1 attenuated the curcumol-induced reduction in glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-As1 reversed the inhibitory effect of curcumol on the binding ability of EZH2 and H3K27me3 modification in the promoter regions of anti-oncogenes. Our results showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-As1-mediated EZH2 activation. Our study offers the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.
目前,常规治疗不足以提高胶质瘤患者的生存率。因此,采用新型个性化治疗方案势在必行。莪术醇是一种从莪术根茎中提取的中药,由于其有益的药理活性而引起了广泛关注。本研究表明,莪术醇抑制了胶质瘤细胞的增殖、转移、自我更新能力和 TMZ 耐药性。接下来,研究了莪术醇抑制胶质瘤的潜在分子机制。我们发现长链非编码 RNA (lncRNA) FOXD2-As1 可能有助于莪术醇对胶质瘤细胞的作用。FOXD2-As1 的过表达减弱了莪术醇诱导的胶质瘤细胞增殖、转移、自我更新能力和 TMZ 耐药性的降低。此外,FOXD2-As1 的强制表达逆转了莪术醇对 EZH2 和 H3K27me3 修饰在抑癌基因启动子区域结合能力的抑制作用。我们的研究结果首次表明,莪术醇通过抑制 FOXD2-As1 介导的 EZH2 激活,有效抑制了胶质瘤细胞的恶性生物学行为和 TMZ 耐药性。我们的研究为利用莪术醇作为治疗胶质瘤的有前途的治疗剂提供了可能性,并可能为这种天然草药的临床应用提供了一种选择。