Zhou Hui, Li Hui, Cao Yan, Sang Xue, Liu Xin
Department of Anesthesiology ， China-Japan Union Hospital of Jilin University, Changchun, Jilin , China , 130033.
J BUON. 2019 Nov-Dec;24(6):2423-2428.
Oral cancer ranks as the 6th most prevalent type of cancer accounting for significant mortality around the world and studies are being directed to develop efficient chemotherapy for oral cancer. In this study the anticancer effects of a carbazole alkaloid Murrayanine were investigated in vitro and in vivo.
Cell counting assay and colony formation assay were used to examine cell viability. DAPI and propidium iodide (PI) staining were used to detect apoptosis. Western blotting was used to examine protein expression. Xenografted mice were used for in vivo study.
The results showed that Murrayanine decreased the viability of the oral cancer SCC-25 cells and exhibited an IC50 of 15 µM. The cytotoxicity of Murrayanine was also investigated on the normal hTERT-OME cells and it was found that this molecule exerted very low toxic effects on these cells exhibiting an IC50 of 92 µM. Murrayanine also caused considerable changes in the morphology of the SCC-25 cells and inhibited their colony forming potential. PI and DAPI staining revealed that Murrayanine prompted apoptosis of the SCC-25 cells. The apoptotic cells from 2.2% in the control increased to around 35% at 30 µM concentration. Moreover, Murrayanine caused increase in the Bax/Bcl-2 ratio and also increased the expression of Caspase-3. Murrayanine also deactivated the AKT/mTOR and Raf/MEK/ERK signalling pathways and suppressed the growth of the xenografted tumors in vivo.
The findings of the present investigation suggest that Murrayanine may prove essential in the development of systemic therapy for oral cancers.
口腔癌是全球第六大常见癌症类型，死亡率较高，目前正在开展研究以开发有效的口腔癌化疗方法。在本研究中，对咔唑生物碱默里任碱的抗癌作用进行了体外和体内研究。
采用细胞计数法和集落形成法检测细胞活力。采用DAPI和碘化丙啶（PI）染色检测细胞凋亡。采用蛋白质免疫印迹法检测蛋白质表达。采用异种移植小鼠进行体内研究。
结果显示，默里任碱降低了口腔癌SCC-25细胞的活力，IC50为15 μM。还对默里任碱对正常hTERT-OME细胞的细胞毒性进行了研究，发现该分子对这些细胞的毒性非常低，IC50为92 μM。默里任碱还引起了SCC-25细胞形态的显著变化，并抑制了它们的集落形成潜力。PI和DAPI染色显示，默里任碱促使SCC-25细胞凋亡。凋亡细胞在对照组中为2.2%，在30 μM浓度下增加到约35%。此外，默里任碱导致Bax/Bcl-2比值增加，同时Caspase-3的表达也增加。默里任碱还使AKT/mTOR和Raf/MEK/ERK信号通路失活，并在体内抑制了异种移植肿瘤的生长。
本研究结果表明，默里任碱可能在口腔癌全身治疗的开发中至关重要。
