Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells.
Autophagy inhibition switches low-dose camptothecin-induced premature senescence to apoptosis in human colorectal cancer cells.
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DOI：
10.1016/j.bcp.2014.05.009
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发表时间：
2014-08
影响因子：
5.8
通讯作者：
Jian-wei Zhang;Shan-shan Zhang;Jian-rui Song;K. Sun;Chen Zong;Qiudong Zhao;Wen-ting Liu;Rong Li;Mengchao Wu;Li-xin Wei
中科院分区：
文献类型：
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作者：
Jian-wei Zhang;Shan-shan Zhang;Jian-rui Song;K. Sun;Chen Zong;Qiudong Zhao;Wen-ting Liu;Rong Li;Mengchao Wu;Li-xin Wei
近年来，一些研究表明衰老的肿瘤细胞对化疗中的凋亡具有抵抗性。它们可能会回到细胞周期，从而成为抗癌治疗的绊脚石。在本研究中，我们发现低剂量喜树碱（camptothecin，CPT）分别通过AMPK-TSC 2-mTOR和ATM-Chk 2-p53-p21途径同时诱导人大肠癌细胞自噬和早衰。重要的是，自噬的抑制可能通过阻断p53/p21通路而显著增加细胞凋亡和大大减轻衰老，这表明自噬在低剂量CPT引起的细胞衰老中起着不可或缺的作用。低剂量CPT和自噬抑制剂的组合，一种导致衰老细胞死亡的方法，将在癌症治疗中具有潜在价值。
Recently, several studies indicated that senescent tumor cells are resistant to apoptosis in chemotherapy. They may return to cell cycle, thus act as stumbling blocks in anticancer treatments. In the present study, we found that, in human colorectal cancer cells, low-dose camptothecin (CPT) simultaneously induced autophagy and premature senescence through AMPK-TSC2-mTOR pathway and ATM-Chk2-p53-p21 pathway respectively. What's important is the suppression of autophagy substantially increased apoptosis and greatly attenuated senescence possibly by blocking p53/p21 pathway, which suggests that autophagy plays an indispensable role in sustaining cell senescence caused by low-dose CPT. The combination of low-dose CPT and autophagy inhibitor, a way to lead senescent cells to die, would be potentially valuable in cancer therapy.