Xue Jie, Wu Yuanyuan, Liu Na
Department of Ultrasonography, Yantai Yuhuangding Hospital, 20# Yuhuangding East Road, Zhifu District, Yantai, 264000 Shandong China.
Department of Ultrasound, Central Hospital of Weihai, 3 West Mi Shan East Road, Wendeng District, Weihai, 264400 Shandong China.
Cell Mol Bioeng. 2018 Sep 6;12(1):99-106. doi: 10.1007/s12195-018-0553-8. eCollection 2019 Feb.
Glioblastoma is the most aggressive cancer that begins within the brain. In clinic, temozolomide was used as anti-tumor drugs for glioblastoma chemotherapy, but showed limited effect. Therefore, how to improve the effect of temozolomide to glioblastoma is urgently needed.
The cell viability of T98G cells was detected by cell counting kit-8 (CCK-8) assay. Apoptosis was detected using the Annexin-V-FITC & PI apoptosis kit and assessed by flow cytometry. The expression levels of Bax, B cell lymphoma 2 (Bcl-2), phos-Jun N-terminal kinases (JNK), phos-extracellular signal-regulated kinases (ERK) and phos-p38 were determined by western blot. The effect of ultrasound and temozolomide combination in mice was determined by survival analysis.
Compared with temozolomide treatment alone, ultrasound and temozolomide combination inhibited the cell viability, and promotes apoptosis of human glioblastoma T98G cells. Bax level increased, while Bcl-2 level decreased in combination group. Mechanically, combination treatment promoted apoptosis JNK and p38 pathways. In mouse glioblastoma model, combination treatment improved overall survival.
Ultrasound enhanced anti-tumor effect of temozolomide in glioblastoma cells JNK and p38 pathways.
胶质母细胞瘤是起源于脑内的最具侵袭性的癌症。在临床上，替莫唑胺被用作胶质母细胞瘤化疗的抗肿瘤药物，但效果有限。因此，迫切需要提高替莫唑胺对胶质母细胞瘤的疗效。
采用细胞计数试剂盒-8（CCK-8）法检测T98G细胞的细胞活力。使用膜联蛋白-V-异硫氰酸荧光素（Annexin-V-FITC）&碘化丙啶（PI）凋亡试剂盒检测凋亡情况，并通过流式细胞术进行评估。通过蛋白质免疫印迹法测定Bax、B细胞淋巴瘤2（Bcl-2）、磷酸化-应激活化蛋白激酶（JNK）、磷酸化-细胞外信号调节激酶（ERK）和磷酸化-p38的表达水平。通过生存分析确定超声与替莫唑胺联合治疗对小鼠的效果。
与单独使用替莫唑胺治疗相比，超声与替莫唑胺联合治疗可抑制人胶质母细胞瘤T98G细胞的细胞活力，并促进其凋亡。联合治疗组中Bax水平升高，而Bcl-2水平降低。从机制上讲，联合治疗通过JNK和p38途径促进凋亡。在小鼠胶质母细胞瘤模型中，联合治疗提高了总体生存率。
超声通过JNK和p38途径增强了替莫唑胺对胶质母细胞瘤细胞的抗肿瘤作用。
