Qing-Kai-Ling Injection Acts Better Than Shen-Fu Injection in Enhancing the Antitumor Effect of Gefitinib in Resistant Non-Small Cell Lung Cancer Models.
Qing-Kai-Ling Injection Acts Better Than Shen-Fu Injection in Enhancing the Antitumor Effect of Gefitinib in Resistant Non-Small Cell Lung Cancer Models.
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清开灵注射液比参附注射液更能增强吉非替尼对耐药非小细胞肺癌模型的抗肿瘤作用
DOI：
10.1155/2021/9911935
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zhang HB
中科院分区：
文献类型：
--
作者：
Yu YY;Zhu YJ;Zou Y;Xiao ZZ;Shi S;Liu YH;Chang XS;Chen YD;Zhang HB
EGFR基因突变的患者通常会对表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）产生新的耐药性，或者在接受EGFR-TKI治疗后对EGFR-TKI产生继发性耐药。具有不同治疗原理的中药与EGFR-TKI联合治疗，在包括耐药性非小细胞肺癌（NSCLC）在内的癌症治疗中发挥着重要作用。然而，中药使用不当可能会导致吉非替尼产生耐药性。因此，评估哪种中医治疗原则应与EGFR-TKIs联合、避免哪种治疗原则，并找出其潜在机制具有重要价值。采用慢病毒转染法检测PC-9细胞中PIK3CA突变基因的过表达，构建PC-9-PIK3CA突变（PC-9-PIK3CA-M）细胞。采用MTT、Annexin V/PI双标、Western blot法检测典型清热灵(QKL)、痰热清(TRQ)或典型温阳药参附(SF)、吉非替尼治疗后PC-9-PIK3CA-M和H1975细胞的细胞增殖、凋亡以及EGFR/PI3K/AKT和EGFR/RAS/RAF/ERK的表达。分别。进行肿瘤异种移植和免疫组织化学实验以证实体外研究结果。与 PC-9 细胞相比，PC-9-PIK3CA-M 细胞对吉非替尼的敏感性较低。 QKL注射液和TRQ注射液（而非SF注射液）与吉非替尼联合诱导PC-9-PIK3CA-M和H1975细胞中细胞生长抑制和细胞凋亡显着增加。 SF注射液拮抗吉非替尼促进癌细胞凋亡的作用。 QKL注射和TRQ注射通过抑制H1975和PC-9-PIK3CA-M细胞中AKT或ERK的磷酸化来增加吉非替尼的敏感性。在 H1975 异种移植小鼠模型体内观察到类似的结果。 QKL和TRQ属于中医凉热治疗原则，宜与吉非替尼联合治疗NSCLC。此外，温阳药SF应避免与EGFR-TKI联合使用。
Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs.
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影响因子：
51.1
作者：
Zhou, Caicun;Wu, Yi-Long;You, Changxuan
通讯作者：
You, Changxuan
DOI：
10.19540/j.cnki.cjcmm.20170523.005
发表时间：
2017-07-01
期刊：
Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica
影响因子：
--
作者：
He, Wei;Cheng, Miao
通讯作者：
Cheng, Miao
影响因子：
--
作者：
Zhang, Feng;Sun, Liang;Chai, Yifeng
通讯作者：
Chai, Yifeng
影响因子：
3.9
作者：
Hu, Cheng;Jiang, Rilei;Zhang, Xu
通讯作者：
Zhang, Xu
影响因子：
6.6
作者：
Sigismund S;Avanzato D;Lanzetti L
通讯作者：
Lanzetti L