20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy
20(S)-ginsenoside Rg3 sensitizes human non-small cell lung cancer cells to icotinib through inhibition of autophagy
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DOI：
10.1016/j.ejphar.2019.02.023
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发表时间：
2019-05-05
影响因子：
5
通讯作者：
Jing, Zhao
中科院分区：
文献类型：
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作者：
Wang, Xiao-Ju;Zhou, Rong-Jin;Jing, Zhao
表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)已成为具有敏感突变的非小细胞肺癌(NSCLC)患者的标准治疗方法。然而，获得性耐药性不可避免地在中位数6-12个月后出现。已有研究表明自噬在EGFR-TKI耐药中起重要作用。20(S)-人参皂苷Rg3(Rg3)被认为通过抑制自噬而使癌细胞对化疗增敏。我们检测了Rg3抑制自噬和增加NSCLC细胞对伊考替尼的敏感性的能力。我们发现，对伊考替尼的反应诱导自噬有助于产生对伊考替尼的耐药性。Rg3能抑制自噬通量，增强NSCLC细胞对伊考替尼的敏感性。对伊考替尼的耐药性也可以通过Rg3诱导的自噬抑制来逆转。RG3抑制自噬增加了带有EGFR激活突变的对伊考替尼敏感和耐药的NSCLC细胞的治疗反应，可能是治疗这种疾病的一种有效的新策略。
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have become a standard therapy for non-small cell lung cancer (NSCLC) patients with sensitive mutations. However, acquired resistance inevitably emerges after a median of 6-12 months. It has been demonstrated that autophagy plays an important role in EGFR-TKI resistance. 20(S)-ginsenoside Rg3 (Rg3) is proposed to sensitize the cancer cells to chemotherapy by inhibiting autophagy. We examined the ability of Rg3 to inhibit autophagy and increase the sensitivity of NSCLC cells to icotinib. We show that the induction of autophagy in response to icotinib contributes to the development of icotinib resistance. Rg3 is capable of inhibiting autophagic flux and enhancing the sensitivity of NSCLC cells to icotinib. The resistance to icotinib could also be reversed through Rg3-induced autophagy inhibition. Autophagy inhibition by Rg3 increases the therapeutic response in both icotinib-sensitive and icotinib-resistant NSCLC cells with an EGFR-activating mutation and may be an effective new treatment strategy for this disease.