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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
副主任中医师,博士。研究方向:中晚期恶性肿瘤的中西医结合治疗。E-mail:liyang2001@126.com
主任药师,硕士生导师。研究方向:中药药理与中药制剂。E-mail:liangqi70@gzucm.edu.cn
收稿日期:2024-08-19,
修回日期:2025-01-18,
录用日期:2025-01-20,
纸质出版日期:2025-02-28
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李阳,陈蕾,张洽淳等.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 Δ[J].中国药房,2025,36(04):440-446.
LI Yang,CHEN Lei,ZHANG Qiachun,et al.Effects of serum containing Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells and its mechanism[J].ZHONGGUO YAOFANG,2025,36(04):440-446.
李阳,陈蕾,张洽淳等.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 Δ[J].中国药房,2025,36(04):440-446. DOI: 10.6039/j.issn.1001-0408.2025.04.09.
LI Yang,CHEN Lei,ZHANG Qiachun,et al.Effects of serum containing Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells and its mechanism[J].ZHONGGUO YAOFANG,2025,36(04):440-446. DOI: 10.6039/j.issn.1001-0408.2025.04.09.
目的
2
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
2
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
2
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
2
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
2
To study the effects of Sanchong tongluo sanjie formula on the proliferation and apoptosis of Lewis lung cancer cells.
METHODS
2
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 post-intervention 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
2
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-1α was decreased significantly in the 20% decoction-containing serum group (
P
<0.05).
CONCLUSIONS
2
Sanchong tongluo sanjie formula can inhibit the proliferation, invasion and metastasis of Lewis lung cancer cells while promoting their apoptosis. The mechanism of action may be related to regulating the PHD2/HIF-1α signaling pathway. Furthermore, the powder demonstrates superior efficacy compared to the decoction, suggesting that they may possess different mechanisms of action.
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