三虫通络散结方含药血清对Lewis肺癌细胞增殖和凋亡的影响及机制  

Effects of serum containing Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells and its mechanism

作　　者：李阳[1] 陈蕾[2] 张洽淳 张晶[1] 冯婧宇 梁奇 LI Yang;CHEN Lei;ZHANG Qiachun;ZHANG Jing;FENG Jingyu;LIANG Qi(Dept.of Oncology,the Seventh Clinical College of Guangzhou University of Chinese Medicine,Guangdong Shenzhen 518133,China;Dept.of Pathology,the Seventh Clinical College of Guangzhou University of Chinese Medicine,Guangdong Shenzhen 518133,China;Dept.of Emergency,the Seventh Clinical College of Guangzhou University of Chinese Medicine,Guangdong Shenzhen 518133,China;Dept.of Pharmacy,the Seventh Clinical College of Guangzhou University of Chinese Medicine,Guangdong Shenzhen 518133,China)

机构地区：[1]广州中医药大学第七临床医学院肿瘤科,广东深圳518133 [2]广州中医药大学第七临床医学院病理科,广东深圳518133 [3]广州中医药大学第七临床医学院急诊科,广东深圳518133 [4]广州中医药大学第七临床医学院药学部,广东深圳518133

出　　处：《中国药房》2025年第4期440-446,共7页China Pharmacy

基　　金：广东省中医药局中医药科研项目(No.20231294);深圳“医疗卫生三名工程”(No.SZZYSM202206005);深圳市宝安区引进高层次医学团队项目(No.202403)。

摘　　要：目的研究三虫通络散结方对Lewis肺癌细胞增殖和凋亡的影响及机制。方法将三虫通络散结方散剂[0.946 g/(kg·d)]、三虫通络散结方汤剂[2.730 g/(kg·d)]和生理盐水灌胃大鼠,将顺铂注射液(4.2 mg/kg)腹腔注射大鼠,以制备散剂血清、汤剂血清、阳性对照血清和阴性对照血清。将Lewis肺癌细胞分为阴性对照血清组、阳性对照血清组及不同浓度(5%、10%、20%)散剂血清组和汤剂血清组,检测干预24、48、72 h时的细胞增殖抑制率,筛选散剂血清和汤剂血清的最佳干预浓度;检测阴性对照血清组、阳性对照血清组、20%散剂血清组、20%汤剂血清组细胞的侵袭能力、迁移能力和凋亡率,以及细胞中血管内皮生长因子(VEGF)、缺氧诱导因子1α(HIF-1α)、脯氨酰羟化酶2(PHD2)、基质金属蛋白酶2(MMP-2)、胞外信号调节激酶(ERK)、c-Jun氨基端激酶(JNK)、p38调控丝裂原活化蛋白激酶(p38 MAPK)蛋白的表达水平。结果20%散剂血清组和20%汤剂血清组干预48 h时细胞的增殖抑制率均不低于50%。与阴性对照血清组比较,20%散剂血清组和20%汤剂血清组细胞的侵袭数量和迁移距离均显著减少,凋亡率均显著升高(P<0.05),且20%散剂血清组细胞凋亡率显著高于20%汤剂血清组(P<0.05);20%散剂血清组细胞中PHD2、p38 MAPK蛋白表达水平均显著升高(P<0.05),20%汤剂血清组细胞中HIF-1α蛋白表达显著降低(P<0.05)。结论三虫通络散结方可抑制Lewis肺癌细胞的增殖、侵袭和迁移,促进其凋亡,作用机制可能与调控PHD2/HIF-1α信号通路相关;且散剂效果优于汤剂,二者可能存在不同的作用机制。OBJECTIVE To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells.METHODS The rats were given Sanchong tongluo sanjie formula powder[0.946 g/(kg·d)],Sanchong tongluo sanjie formula decoction[2.730 g/(kg·d)],and normal saline intragastrically,and injected with Cisplatin injection(4.2 mg/kg)intra-peritoneally to prepare powder-containing serum,decoction-containing serum,positive control serum and negative control serum.Lewis lung cancer cells were divided into negative control serum group,positive control serum group,and 5%,10%,20%drug-containing serum groups.The cell proliferation inhibition rates at 24,48,and 72 hours postintervention were measured to screen the optimal intervention concentrations of powder-containing serum and decoction-containing serum.The cell invasion ability,metastasis ability and apoptotic rate were detected in the negative control serum group,positive control serum group,20%powder-containing serum group,and 20%decoction-containing serum group.Protein expressions of vascular endothelial growth factor(VEGF),hypoxia-inducible factor-1α(HIF-1α),prolyl hydroxylase-2(PHD2),matrix metalloproteinase-2(MMP-2),extracellular regulated protein kinases(ERK),c-Jun N-terminal kinase(JNK)and p38 mitogen-activated protein kinase(p38 MAPK)were detected.RESULTS The cell proliferation inhibition rates for both the 20%powder-containing serum group and the 20%decoction-containing serum group,when intervened for 48 hours,were not less than 50%.Compared with negative control serum group,the number of invasive Lewis lung cancer cells and migration distance were decreased significantly,while the apoptotic rate was increased significantly(P<0.05);the apoptotic rate in the 20%powder-containing serum group was significantly higher than 20%decoction-containing serum group(P<0.05).The protein expressions of PHD2 and p38 MAPK were increased significantly in the 20%powder-containing serum group(P<0.05),while the protein expression of HIF-1αwas decreased si

关 键 词：三虫通络散结方 LEWIS肺癌细胞 增殖 侵袭 转移 凋亡 PHD2/HIF-1α通路 

分 类 号：R965[医药卫生—药理学]