Cai Bo, Ma Limin, Nong Shaojun, Wu You, Guo Xin, Pu Jinxian
Department of Urology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
Department of Urology, The First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215001, P.R. China.
Oncol Lett. 2018 Nov;16(5):6019-6025. doi: 10.3892/ol.2018.9401. Epub 2018 Sep 5.
Human bladder cancer is one of the most aggressive tumours known and has shown resistance to traditional chemotherapy, which depends heavily on DNA-damaging drugs. β-elemene is one of the least cytotoxic antitumor agents that are extracted from Curcuma aromatica salisb and it exhibits antitumor effects in many carcinomas. β-elemene has attracted the attention of clinicians and scientists worldwide due to its few side effects and limited effect on the bone marrow. However, the antitumor mechanism of β-elemene remains largely unstudied. In the present study, the expression of the AKT serine/threonine kinase (AKT) signaling pathway in bladder cancer and normal bladder tissue was investigated, and the influence of β-elemene on bladder cancer cells and the mechanisms involved were assessed. The results showed that phosphatase and tensin homolog deleted on chromosome ten (PTEN) was downregulated and phosphorylated-AKT (pAKT) was overexpressed in human bladder cancer. β-elemene significantly suppressed the viability of bladder cancer cells, while leaving normal bladder cells unaffected. In addition, there was an increased number of apoptotic bladder cancer cells following β-elemene treatment, and a significant reduction in cell invasion and migration. Subsequent western blot analyses revealed that bladder cancer cells treated with β-elemene had increased PTEN expression and decreased expression of pAKT. Taken together, these results suggest that β-elemene has an antitumor effect in bladder cancer cells through the upregulation of PTEN and suppression of AKT phosphorylation.
人类膀胱癌是已知的最具侵袭性的肿瘤之一,并且已显示出对传统化疗具有抗性,传统化疗严重依赖于DNA损伤药物。β-榄香烯是从莪术中提取的细胞毒性最小的抗肿瘤药物之一,它在许多癌症中都表现出抗肿瘤作用。由于其副作用少且对骨髓影响有限,β-榄香烯已引起全球临床医生和科学家的关注。然而,β-榄香烯的抗肿瘤机制在很大程度上仍未得到研究。在本研究中,我们调查了膀胱癌和正常膀胱组织中AKT丝氨酸/苏氨酸激酶(AKT)信号通路的表达,并评估了β-榄香烯对膀胱癌细胞的影响及其相关机制。结果表明,在人类膀胱癌中,第10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)表达下调,而磷酸化AKT(pAKT)过表达。β-榄香烯显著抑制膀胱癌细胞的活力,而对正常膀胱细胞没有影响。此外,β-榄香烯处理后凋亡的膀胱癌细胞数量增加,细胞侵袭和迁移显著减少。随后的蛋白质印迹分析显示,用β-榄香烯处理的膀胱癌细胞中PTEN表达增加,pAKT表达降低。综上所述,这些结果表明β-榄香烯通过上调PTEN和抑制AKT磷酸化对膀胱癌细胞具有抗肿瘤作用。