Effect of Protein Kinase C Inhibitor Enzastaurin on Growth of Gefitinib-resistant Human Non-small Cell Lung Cancer Cell Lines
- VernacularTitle:蛋白激酶C抑制药 enzastaurin对吉非替尼耐药的人非小细胞肺癌细胞株生长的影响
- Author:
Yunjie SHEN
;
Jun ZHU
;
Jiaqin GU
;
Huifang SHA
- Publication Type:Journal Article
- Keywords:
Non-small cell lung cancer;
Gefitinib;
Drug resistant;
Protein kinase C inhibitor;
Enzastaurin
- From:
China Pharmacist
2014;(4):529-533
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the effect of a novel targeted agent enzastaurin alone or in combination with gefitinib on ge-fitinib-resistant human non-small cell lung cancer cells to explore the rational drug combination. Methods: CCK-8 assay was used to measure the cell proliferation. Combination index ( CI) was calculated by Chou-Talalay method to assess the efficacy of the combination therapy. The flow cytometry (FCM) was used to analyze the change in the cell cycle. Results:In 72h, the IC50 value of gefitinib and enzastaurin for the lung cancer NCI-H460 cells was 6. 99μmol·L-1 (95%CI:3. 55-13. 79μmol·L-1 ) and 7. 25μmol·L-1 (95%CI:4. 77-1. 02 μmol·L-1), respectively. The inhibition effect on the cell proliferation was stronger in the combination treatment than that in the monotherapy (P<0. 05), and the simultaneous treatment showed the most significant inhibition effect (P<0. 01). The IC50 value of gefitinib for H460 cells in the simultaneous administration group, the sequential administration group with gefitinib used first and the sequential administration group with enzastaurin used first was 0.006 μmol·L-1(95%CI:0.002-0.020μmol·L-1), 0.02μmol·L-1(95%CI:0.011-0.037 μmol·L-1) and 0.085 μmol·L-1(95% CI:0.042-0.170μmol·L-1, respectively. The CI of the simultaneous administration group was lower than one when the gefitinib concentration was above 0. 05μmol·L-1 . The cell cycle distribution result indicated that the simultaneous administration group had significantly increased G0/G1 proportion (P<0. 05) and induced cell cycle arrest at G1 phase. Conclusion:Protein kinase C inhibitor enzastaurin combined with EGFR inhibitor gefitinib shows a synergistic effect, suggesting that the combination treatment of the two drugs might be a new strategy for the follow-up therapy of gefitinib-resistant non-small cell lung cancer.
