Background. Pancreatic carcinoma is a malignant tumor with a high fatality rate, and the increased resistance of pancreatic carcinoma to chemotherapy has become a difficult problem in clinical practice. Hence, it is imperative to develop an effective treatment for pancreatic cancer. Sestrins are a class of stress-induced proteins that have antioxidation functions, regulating cell growth and metabolism. Curcumin is a natural pigment isolated from turmeric. Several studies have also suggested that this molecule has multiple pharmacological effects, such as anti-inflammatory, antioxidant, and antitumor effects. However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. Our aim was to observe the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms. Methods. Lentiviral infection, real-time fluorescence quantitative PCR assays, Cell Counting Kit-8 assays, real-time cell analysis technology, colony formation assays, wound healing assays, Transwell invasion assays, protein extraction, and western blots (WBs) were used to evaluate the effect of curcumin combined with sestrin2 on the proliferation, invasion, and migration of pancreatic carcinoma cells. Results. The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer. In addition, we determined that sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1. Conclusion. These findings clarify that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer.

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姜黄素与Sestrin2协同抑制胰腺癌生长的机制研究

背景. 胰腺癌是一种致死率较高的恶性肿瘤，胰腺癌对化疗的耐药性增加已成为临床上的难题。因此，开发一种有效的胰腺癌治疗方法势在必行。Sestrins 是一类具有抗氧化功能、调节细胞生长和代谢的应激诱导蛋白。姜黄素是一种从姜黄中分离出来的天然色素。一些研究还表明，这种分子具有多种药理作用，例如抗炎、抗氧化和抗肿瘤作用。但姜黄素与sestrin家族协同抑制肿瘤的研究尚不充分，机制尚不清楚。方法。慢病毒感染、实时荧光定量 PCR 测定、细胞计数 Kit-8 测定、实时细胞分析技术、集落形成测定、伤口愈合测定、Transwell 侵袭测定、蛋白质提取和蛋白质印迹 (WBs) 用于评估姜黄素联合sestrin2对胰腺癌细胞增殖、侵袭和迁移的影响。结果。结果显示姜黄素与sestrin2协同作用显着抑制胰腺癌。此外，我们确定 sestrin2 与姜黄素协同作用，通过特异性靶向 Nrf2/Keap1/HO-1/NQO-1 来抑制胰腺癌。结论. 这些发现阐明姜黄素介导的 sestrin2 协同靶向治疗是胰腺癌的潜在有价值的治疗方法。