Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, Zhejiang Provincial Top Key Discipline in Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. of China.
Department of Hepatobiliary Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, P.R. of China.
Curr Cancer Drug Targets. 2023;23(9):731-741. doi: 10.2174/1568009623666230328123915.
Pancreatic cancer is highly fatal and its incidence is rising worldwide. Its poor prognosis is attributed to a lack of effective diagnostic and therapeutic strategies. Dihydrotanshinone I (DHT), a phenanthrene quinone liposoluble compound from (Danshen), exerts anti-tumor effects by inhibiting cell proliferation, enhancing apoptosis, and inducing cell differentiation. However, its effects on pancreatic cancer are unclear. > Methods: The role of DHT in the growth of tumor cells was explored using real-time cell analysis (RTCA), colony formation assay, and CCK-8. The effects of DHT on tumor cells invasion as well as migration were assessed by Transwell and migration assays. Expressions of pro-apoptosis and metastasis factors in tumor cells were examined using western blot. Tumor apoptosis rates were studied using flow cytometry. The anticancer effect of DHT was assessed by tumor transplantation into nude mice.
Our analyses show that DHT has a suppressive role in epithelial-mesenchymal transition (EMT), invasiveness, proliferation, as well as migratory ability of Patu8988 and PANC-1 cells Hedgehog/Gli signaling. Moreover, it drives apoptosis caspases/BCL2/BAX signaling. Experiments in nude mice transplanted with tumors have shown DHT to have anticancer effects . > Conclusion: Our data show that DHT effectively suppresses pancreatic cancer cell proliferation as well as metastasis, and induces apoptosis Hedgehog/Gli signaling. These effects have been reported to be dose- and time-dependent. Therefore, DHT can be exploited as a potential treatment for pancreatic cancer.>.
胰腺癌具有较高的致死率，其发病率在全球范围内呈上升趋势。其预后不良归因于缺乏有效的诊断和治疗策略。丹参中的二氢丹参酮 I（DHT）是一种菲醌脂溶性化合物，通过抑制细胞增殖、增强细胞凋亡和诱导细胞分化发挥抗肿瘤作用。然而，其对胰腺癌的作用尚不清楚。
采用实时细胞分析（RTCA）、集落形成实验和 CCK-8 法探讨 DHT 对肿瘤细胞生长的作用。通过 Transwell 和迁移实验评估 DHT 对肿瘤细胞侵袭和迁移的影响。采用 Western blot 检测肿瘤细胞中促凋亡和转移因子的表达。采用流式细胞术研究肿瘤细胞的凋亡率。通过肿瘤移植到裸鼠中评估 DHT 的抗癌作用。
我们的分析表明，DHT 对 Patu8988 和 PANC-1 细胞的上皮间质转化（EMT）、侵袭性、增殖和迁移能力具有抑制作用 Hedgehog/Gli 信号通路。此外，它通过 caspase/BCL2/BAX 信号通路诱导细胞凋亡。在荷瘤裸鼠实验中，DHT 显示出抗癌作用。
我们的数据表明，DHT 能有效抑制胰腺癌细胞的增殖和转移，并诱导 Hedgehog/Gli 信号通路诱导细胞凋亡。这些作用呈剂量和时间依赖性。因此，DHT 可被开发为治疗胰腺癌的潜在药物。
