摘要
目的:探讨青蒿琥酯通过Toll样受体(TLR)4/核因子κB(NF-κB)信号通路抑制人胃癌裸鼠移植瘤生长及对增殖细胞核抗原(PCNA)和锌指蛋白(ZNF)139表达的影响。方法:40只BALB/c裸鼠接种人胃癌细胞株SGC7901建模,随机分为模型组(0.9%氯化钠溶液)、顺铂组(顺铂4 mg/kg)、青蒿琥酯组(注射用青蒿琥酯100 mg/kg)和联合组(顺铂4 mg/kg+注射用青蒿琥酯100 mg/kg),瘤体内注射给药,1周2次,持续4周。记录治疗期间裸鼠食欲、活动度和精神状态等情况以及肿瘤生长情况;采用苏木精-伊红染色法进行病理检测,噻唑蓝法(MTT)检测原代细胞生长,逆转录聚合酶链反应检测PCNA、ZNF139、TLR4、髓样分化因子(MyD88)和NF-κB mRNA表达水平,蛋白质印迹法检测相对蛋白表达水平。结果:与模型组比较,顺铂组、青蒿琥酯组和联合组平均瘤重明显降低;与顺铂组比较,青蒿琥酯组平均瘤重升高,抑瘤率降低;联合组平均瘤重低于顺铂组和青蒿琥酯组,抑瘤率高于顺铂组和青蒿琥酯组,差异均有统计学意义(P<0.05)。培养48 h后,顺铂组、青蒿琥酯组和联合组吸光度(OD)值均低于模型组;联合组OD值低于顺铂组和青蒿琥酯组,抑制率高于顺铂组和青蒿琥酯组,差异均有统计学意义(P<0.05)。与模型组比较,顺铂组、青蒿琥酯组和联合组PCNA2、ZNF139、TLR4、MyD88和NF-κB mRNA及相对蛋白表达水平均明显降低;顺铂组PCNA2、ZNF139、TLR4、MyD88和NF-κB mRNA及相对蛋白表达水平明显低于青蒿琥酯组;联合组PCNA2、ZNF139、TLR4、MyD88和NF-κB mRNA及相对蛋白表达水平明显低于顺铂组和青蒿琥酯组,差异均有统计学意义(P<0.05)。结论:青蒿琥酯可能通过抑制TLR4/NF-κB信号通路,抑制人胃癌细胞的生长,同时能下调PCNA和ZNF139的表达,影响肿瘤增殖、侵袭和转移。
OBJECTIVE: To explore the inhibition of artesunate on growth of transplanted human gastric cancer through Toll-like receptor(TLR) 4/nuclear factor κB(NF-κB) signaling pathway and its effects on expression of proliferating cell nuclear antigen(PNCA) and ZNF139. METHODS: Forty BALB/c nude mice were inoculated with human gastric cancer cell line SGC7901 for modeling and randomly divided into the model group(0.9% sodium chloride solution), cisplatin group(cisplatin 4 mg/kg), artesunate group(artesunate for injection 100 mg/kg) and combination group(cisplatin 4 mg/kg + artesunate for injection 100 mg/kg). Intratumoral injection was performed twice a week for 4 weeks. The appetite, activity, mental state and tumor growth of nude mice were recorded. Hematoxylin and Eosin staining were used for pathological detection, MTT assay was used to detect the growth of primary cells, reverse transcriptase polymerase chain reaction was used to detect the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB, and Western blotting was used to detect the relative protein expression. RESULTS: Compared with the model group, the average tumor weight of cisplatin group, artesunate group and combined group decreased significantly;compared with the cisplatin group, the average tumor weight increased and the tumor inhibition rate decreased in the artesunate group;the average tumor weight of the combination group was lower than that of the cisplatin group and artesunate group, and the tumor inhibition rate was higher than that of the cisplatin group and artesunate group, with statistically significant differences(P<0.05). After 48 h of culture, the OD values of cisplatin group, artesunate group and combination group were lower than those of model group;the OD value of the combination group was lower than that of the cisplatin group and artesunate group, and the inhibition rate was higher than that of the cisplatin group and artesunate group, with statistically significant differences(P<0.05). Compared with the model group, the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB in the cisplatin group, artesunate group and combination group significantly decreased;the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB of the cisplatin group were significantly lower than those of the artesunate group;the mRNA expression of PCNA, ZNF139, TLR4, MyD88 and NF-κB of the combination group were significantly lower than those of the cisplatin group and artesunate group, with statistically significant differences(P<0.05). CONCLUSIONS: Artesunate may inhibit the growth of human gastric cancer through inhibiting the TLR4/NF-κB signaling pathway, which can down-regulate the expression of PCNA and ZNF139 and affect the proliferation, invasion and metastasis of tumor.
作者
刘晓蕾
马立东
张朵朵
LIU Xiaolei;MA Lidong;ZHANG Duoduo(Dept.of Geriatrics,the First Hospital of Handan,Hebei Handan 056000,China;Dept.of Gastroenterology,the First Hospital of Handan,Hebei Handan 056000,China;Dept.of Internal Medicine,Hebei Special Care Hospital,Shijiazhuang 050062,China)
出处
《中国医院用药评价与分析》
2022年第10期1201-1205,共5页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
河北省医学科学课题研究计划项目(No.20220491)。
