The effect and mechanism of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors in patients of non-small cell lung cancers / 中国医师进修杂志
Chinese Journal of Postgraduates of Medicine
; (36): 923-927, 2017.
Article
in Zh
| WPRIM
| ID: wpr-658949
Responsible library:
WPRO
ABSTRACT
Objective To investigate the effect of autophagy on acquired secondary resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKI) in patients of non-small cell lung cancers (NSCLC). Methods Ninety-eight patients with pathological confirmation of lung adenocarcinoma were selected, and they were treated with EGFR-TKI. Among them, 49 patients were sensitive to EGFR-TKI, (EGFR-TKI sensitive group), and the others were resistant (EGFR-TKI resistant group). The expressions of mTOR, Beclin-1 and LC3 were detected by immunohistochemistry, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot method. Results The immunohistochemistry results showed that the Beclin-1 and LC3 positive expression rates of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:24.49%(12/49) vs. 83.67%(41/49) and 22.45% (11/49) vs. 85.71% (42/49), and the mTOR positive expression rate was significantly higher than that in EGFR-TKI sensitive group: 77.55% (38/49) vs. 20.41% (10/49), and there were statistical differences (P<0.05). The RT-PCR results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group: 0.723 ± 0.029 vs. 2.542 ± 0.104 and 0.886 ± 0.034 vs. 2.234 ± 0.164, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group:2.142 ± 0.132 vs. 0.638 ± 0.031, and there were statistical differences (P<0.05). The Western blot results showed that the Beclin-1 and LC3 positive expressions of tumor tissue in EGFR-TKI resistant group were significantly lower than those in EGFR-TKI sensitive group:0.315 ± 0.037 vs. 1.226 ± 0.017 and 0.420 ± 0.016 vs. 1.023 ± 0.014, and the mTOR positive expression was significantly higher than that in EGFR-TKI sensitive group: 0.986 ± 0.032 vs. 0.282 ± 0.021, and there were statistical differences (P<0.05). In EGFR-TKI sensitive group and EGFR-TKI resistant group, the Beclin-1 and LC3 showed positive correlation, and the Beclin1 and LC3 showed negative correlation with mTOR. Conclusions The signaling molecules of autophagy play an important role in secondary resistance to EGFR-TKI in patients of NSCLC. As a regulation mechanism of autophagy, mTOR takes part in the procedure of resistance to EGFR-TKI, and give a new biological marker of the predication of drug resistance. Meanwhile, it gives a new target of drug resistance reversal and individualized treatment.
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WPRIM
Language:
Zh
Journal:
Chinese Journal of Postgraduates of Medicine
Year:
2017
Type:
Article