背景:膀胱癌,是全球第10大最常见的癌症,每年有超过60万人被诊断,造成20万人死亡。青蒿素及其衍生物是安全的化合物,最近被证明在体内具有有效的抗肿瘤作用,通过抑制癌细胞生长。这项研究的目的是评估青蒿素作为单独的癌症治疗和作为高级尿路上皮癌的顺铂治疗前的治疗效果。
方法:将60只雄性白化小鼠分为6组,BBN用于诱导膀胱癌。血样进行肾功能和全血细胞计数检测,收集肾脏和膀胱组织进行组织病理学检查。收集膀胱组织的总RNA,和FGFR3,HRAS的基因表达,使用qRT-PCR定量P53和KDM6A。
结果:与诱发癌症组相比,结果显示,FGFR3表达水平在仅用青蒿素治疗的诱导癌组和在顺铂之前用青蒿素预处理的诱导癌组下调约0.86倍和0.4倍,分别,与HRAS下调约9.54倍和9.05倍一致,分别。然而,P53表达水平上调约0.68倍和0.84倍,分别,与KDM6A表达并行,向上调节~0.95倍和5.27倍,分别。此外,血清肌酐和尿素水平在单独使用青蒿素治疗的诱导癌症组和顺铂前使用青蒿素治疗的诱导癌症组显著下降,而用顺铂治疗的诱导癌症组,其水平显着增加。此外,Hb,PLT,红细胞,在单独使用青蒿素治疗和在顺铂之前使用青蒿素预处理的两个癌症组中,WBC计数均得到改善。组织学上,在肾脏组织中,青蒿素预处理可显着减少顺铂引起的肾损伤。而青蒿素治疗膀胱组织癌症将浸润性尿路上皮癌逆转为中度尿路上皮发育不良。
结论:这项研究表明,青蒿素在逆转高级别尿路上皮癌的多步骤癌变过程中具有显着的作用,并且可以增强使用青蒿素预处理的顺铂治疗效果。
BACKGROUND: Urinary bladder cancer, is the 10th most common global cancer, diagnosed in over 600,000 people causing 200,000 deaths annually. Artemisinin and its derivatives are safe compounds that have recently been proven to possess potent anti-tumor effects in vivo, through inhibition of cancer cell growth. The aim of this study is to assess the efficiency of artemisinin as a cancer treatment alone and as a pre-treatment fore cisplatin therapy for high grade urothelial carcinoma.
METHODS: Sixty male albino mice were divided into six groups, and BBN was used to induce urinary bladder cancer. Blood samples were tested for renal functions and complete blood counts, kidney and urinary bladder tissues were harvested for histopathological examination. Total RNAs from urinary bladder tissues was collected, and gene expression of FGFR3, HRAS, P53, and KDM6A was quantified using qRT-PCR.
RESULTS: Compared to the induced cancer group, the results revealed that FGFR3 expression levels were down-regulated in the induced cancer group treated by artemisinin only and the induced cancer group pre-treated with artemisinin prior to cisplatin by ~ 0.86-fold and 0.4-folds, respectively, aligning with HRAS down-regulation by ~ 9.54-fold and 9.05-fold, respectively. Whereas, P53 expression levels were up-regulated by ~ 0.68-fold and 0.84-fold, respectively, in parallel with KDM6A expression, which is up-regulated by ~ 0.95-folds and 5.27-folds, respectively. Also, serum creatinine and urea levels decreased significantly in the induced cancer group treated by artemisinin alone and the induced cancer group pre-treated with artemisinin prior to cisplatin, whereas the induced cancer group treated by cisplatin their levels increased significantly. Moreover, Hb, PLT, RBC, and WBC counts improved in both cancer groups treated by artemisinin alone and pre-treated with artemisinin prior to cisplatin. Histologically, in kidney tissues, artemisinin pre-treatment significantly reduced renal injury caused by cisplatin. While Artemisinin treatment for cancer in bladder tissues reverted invasive urothelial carcinoma to moderate urothelial dysplasia.
CONCLUSIONS: This study indicates that artemisinin demonstrated a significant effect in reversal of the multi-step carcinogenesis process of high grade urothelial carcinoma and could enhance the effect of cisplatin therapy using artemisinin pre-treatment.