Hu Gaoyu, Cao Cong, Deng Zhihua, Li Jun, Zhou Xihan, Huang Zansong, Cen Chao
Department of Gastroenterology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China.
Department of General Medicine, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi 533000, P.R. China.
Oncol Lett. 2021 Jan;21(1):66. doi: 10.3892/ol.2020.12327. Epub 2020 Nov 25.
Matrine, an alkaloid isolated from , promotes tumor cell apoptosis and strengthens the anticancer capacity of chemotherapeutic drugs. The present study aimed to investigate the inhibitory effect and underlying mechanism of matrine in combination with cisplatin on liver cancer progression. Tumor progression was studied in nude mice. The human liver cancer cell line HepG2 was injected into BALB/c nude mice subcutaneously to establish a tumor model. Mice were subsequently treated with matrine, cisplatin, matrine + cisplatin or normal saline. Nude mice and tumor growth were monitored. Tumors were excised and the expression of survivin, caspase-3, caspase-7 and caspase-9 was detected by immunohistochemistry. Western blotting was used to determine the expression of survivin, caspase-3, caspase-7, caspase-9 and X-linked inhibitor of apoptosis protein (XIAP) in tumor tissues. The results demonstrated that matrine exerted anticancer effects in liver cancer-transplanted tumors, as evidenced by decrease in tumor weight and volume. Furthermore, the tumor inhibition rate in mice treated with matrine + cisplatin was 83.3%, whereas it was of 37.5 and 75% in mice treated with matrine or cisplatin alone, respectively. In addition, the expression of survivin and XIAP was significantly downregulated, whereas the expression of caspase-3, caspase-7 and caspase-9 was significantly upregulated in tumor tissues from nude mice treated with matrine + cisplatin, compared with those treated with cisplatin, matrine or normal saline. These findings suggested that the combination of matrine and cisplatin may promote tumor cell apoptosis in liver cancer by activating the caspase apoptosis pathway and suppressing the survivin-associated inhibition of caspase-9.
苦参碱是从[具体来源未给出]中分离出的一种生物碱,可促进肿瘤细胞凋亡并增强化疗药物的抗癌能力。本研究旨在探讨苦参碱联合顺铂对肝癌进展的抑制作用及其潜在机制。在裸鼠中研究肿瘤进展情况。将人肝癌细胞系HepG2皮下注射到BALB/c裸鼠体内以建立肿瘤模型。随后,小鼠分别接受苦参碱、顺铂、苦参碱+顺铂或生理盐水治疗。监测裸鼠和肿瘤生长情况。切除肿瘤,通过免疫组织化学检测存活素、半胱天冬酶-3、半胱天冬酶-7和半胱天冬酶-9的表达。采用蛋白质印迹法测定肿瘤组织中存活素、半胱天冬酶-3、半胱天冬酶-7、半胱天冬酶-9和凋亡蛋白X连锁抑制因子(XIAP)的表达。结果表明,苦参碱对肝癌移植瘤具有抗癌作用,表现为肿瘤重量和体积的降低。此外,苦参碱+顺铂治疗组小鼠的肿瘤抑制率为83.3%,而单独使用苦参碱或顺铂治疗组小鼠的肿瘤抑制率分别为37.5%和75%。此外,与顺铂、苦参碱或生理盐水治疗组相比,苦参碱+顺铂治疗的裸鼠肿瘤组织中存活素和XIAP的表达显著下调,而半胱天冬酶-3、半胱天冬酶-7和半胱天冬酶-9的表达显著上调。这些发现提示,苦参碱与顺铂联合应用可能通过激活半胱天冬酶凋亡途径并抑制存活素相关的半胱天冬酶-9抑制作用来促进肝癌细胞凋亡。