复方皂刺汤对顺铂联合吉西他滨抑制非小细胞肺癌生长的作用及其机制研究

doi:10.3969/j.issn.1004-616x.2022.05.006

摘要/Abstract

摘要： 目的：探讨复方皂刺汤对顺铂联合吉西他滨抑制非小细胞肺癌生长的作用及其机制。方法：50只SPF级BALB/c裸鼠通过右前肢腋窝靠背部接种A549细胞悬液制备非小细胞肺癌模型，造模成功后随机分为模型组、复方皂刺汤组、吉西他滨联合铂类(GP)方案化疗组、顺铂组、复方皂刺汤联合GP方案化疗组，共5组。模型组每天灌胃生理盐水(0.01 mL/g)；复方皂刺汤组每天灌胃复方皂刺汤(1 mL/只)；GP方案化疗组每3天腹腔注射1次顺铂(2 mg/kg)和吉西他滨(50 mg/kg)；顺铂组每3天腹腔注射1次顺铂(2 mg/kg)；复方皂刺汤联合 GP方案化疗组每天灌胃复方皂刺汤(1 mL/只)，并且每3天腹腔注射1次顺铂(2 mg/kg)和吉西他滨(50mg/kg)。各组共给药治疗21 d。分别于给药第3、7、14、21天用游标卡尺测量肿瘤直径，处死裸鼠后，测量瘤质量；采用TUNEL染色观察肿瘤细胞凋亡情况；免疫组织化学法检测肿瘤组织Ki67、CD31、α-SMA和VEGF蛋白的表达；ELISA法检测血清IL-4、IL-6和TNF-α浓度；Western blot法检测肿瘤组织Bax、Bcl-2、Caspase-3蛋白的表达。结果：给药第21天时，与模型组比较，其他 4组裸鼠肿瘤体积、瘤质量明显减小，其中复方皂刺汤联合 GP方案化疗组肿瘤体积、瘤质量最小(P<0.05)；与其他 4组比较，复方皂刺汤联合GP方案化疗组细胞凋亡率、Bax、Caspase-3蛋白表达明显升高，Ki67、Bcl-2蛋白表达明显降低(P<0.05)；与模型组、复方皂刺汤组、GP方案化疗组比较，复方皂刺汤联合GP方案化疗组IL-6、TNF-α含量及CD31、α-SMA、VEGF蛋白表达明显降低，IL-4含量明显升高(P<0.05)。结论：复方皂刺汤在增强顺铂联合吉西他滨抑制非小细胞肺癌生长方面具有肯定作用，其机制可能与抑制血管生成、诱导细胞凋亡有关。

关键词: 非小细胞肺癌, 复方皂刺汤, 顺铂, 吉西他滨, 血管生成, 细胞凋亡

Abstract: OBJECTIVE: To investigate effects from Zaoci decotion in combinations with cisplatin and gemcitadine on growth inhibition of non-small cell lung cancers.METHODS: Fifty SPF-grade BALB/c nude mice were inoculated with A549 cell suspension in the axilla of the right forelimb against the back and used as a non-small cell lung cancer model.After successful modeling,inoculated mice were randomly divided into several groups:model,Zaoci decotion,gemcitabine combined with cisplatin (GP),cisplatin,and Zaoci decotion combined with GP.The model group was gavaged with saline (0.01 mL/g) per day;Zaoci decotion group gavaged with daily saponin soup (1 mL/mouse);GP group intraperitoneal injection with cisplatin (2 mg/kg) and gemcitabine (50 mg/kg) once every 3 days;cisplatin group intraperitoneal injection with cisplatin (2 mg/kg) for 1 time every 3 days;Zaoci decotion combined with GP regimen group daily gavage with Zaoci decotion (1 mL/mouse) and intraperitoneal injection with cisplatin (2 mg/kg) and gemcitabine (50 mg/kg) every 3 days.A total of 21 d of treatment was administered to each group.Tumor diameters were measured by vernier calipers at 3 d,7 d,14 d and 21 d of administrations;their weights were recorded after execution of the mice;tumor cell apoptoses were observed by TUNEL staining;tumor tissue Ki67,CD31,α-SMA and VEGF expressions were detected by immunohistochemistry;serum IL-4,IL-6 and TNF-α concentrations were detected by ELISA;tumor tissue Bax,Bcl-2 and Caspase-3 protein expressions were detected by Western blot.RESULTS: On the 21st day of administration,compared with the model group,tumor volumes and tumor weights in the Zaoci decotion,GP,cisplatin,and Zaoci decotion combined with GP groups were reduced significantly.The tumor volumes and tumor weights of the Zaoci decotion combined with GP group were the smallest (P<0.05).The apoptosis rates,Bax and Caspase-3 protein expressions were significantly higher,and Ki67 and Bcl-2 protein expressions were significantly lower in the Zaoci decotion combined with GP compared with the model group,the Zaoci decotion,the GP,and the cisplatin groups (P<0.05).Compared with the model group,the Zaoci decotion and the GP groups showed significantly lower IL-6 and TNF-α contents,and expressions of CD31,α-SMA and VEGF proteins (P<0.05).The contents of IL-4 were significantly higher in the Zaoci decotion combined with GP group (P<0.05).CONCLUSION: Zaoci decotion showed significant enhancing effects on the growth inhibition of non-small cell lung cancer by cisplatin combined with gemcitabine.The mechanism may be related to the inhibition of angiogenesis and induction of apoptosis.

Key words: non-small cell lung cancer, compound Zaoci decotion, cisplatin, gemcitabine, angiogenesis, apoptosis

中图分类号:

R734.2

齐建考, 汤肖, 孙世辉, 寇艳方, 崔志勤. 复方皂刺汤对顺铂联合吉西他滨抑制非小细胞肺癌生长的作用及其机制研究[J]. 癌变·畸变·突变, 2022, 34(5): 366-372,403.

QI Jiankao, TANG Xiao, SUN Shihui, KOU Yanfang, CUI Zhiqin. Growth inhibition of non-small cell lung cancers by Zaoci decotion in combination with cisplatin and gemcitabine[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2022, 34(5): 366-372,403.

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