木香对非小细胞肺癌中吉非替尼耐药的影响

Effect of Radix Aucklandiae on the resistance of Gefitinib in non-small cell lung cancer

目的观察云木香和印木香联合吉非替尼对非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI)耐药线虫模型的影响,初步探讨其主要有效成分。方法采用基因型人体化(LET-23::hEGFR-TK[T790M-L858R])的秀丽隐杆线虫突变体jgIs25,确定云木香和印木香的有效抑制浓度,并利用高效液相色谱法(Hypersil BDS C18250 mm×4.6 mm,5μm,检测波长:220 nm)初步确定其有效活性成分。结果当印木香浓度在100~750μg/mL、云木香浓度在500~750μg/mL时,对秀丽隐杆线虫突变体jgIs25阴门表达影响的差异有高度统计学意义(P<0.01),初步推测活性单体为木香烃内酯、去氢木香内酯。结论木香联合吉非替尼可逆转非小细胞肺癌EGFR-TKI耐药,为后续临床研究提供基础。

Objective To observe the effect of Saussurea costus and Indian costus combined with Gefitinib on the model of C.elegans which was resistant to epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI),and to research the main effective active components.Methods Genotyped anthropogenic(LET-23::hEGFR-TK[T790M-L858R])C.elegans mutant jgIs25 was used to ensure the effective inhibitory concentration of Saussurea costus and Indian costus.The effective active components were preliminarily determined by HPLC(Hypersil BDS C18250 mm×4.6 mm,5μm,detection wavelength:220 nm).Results There were significant differences in the vulva expression of C.elegans jgIs25,when the concentration of Indian costus was 100-750μg/mL and Saussurea costus was 500-750μg/mL(P<0.01).It was preliminarily speculated that the active monomers were costunolide and dehydrocostus lactone.Conclusion Radix Aucklandiae combined with Gefitinib can reverse EGFR-TKI resistance in non-small cell lung cancer.It can provide the basis for the follow-up clinical research.