Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy
| Autor: | Tianshu Liu, Jie Huang, Zhangfan Mao, Zhifu Mao, Juntao Liu, Songping Xie |
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| Rok vydání: | 2014 |
| Předmět: |
Cell type
Lung Neoplasms Biophysics Notch signaling pathway Antineoplastic Agents Cell Separation Adenocarcinoma Biology Stem cell marker Biochemistry Antigens CD Cancer stem cell Cell Line Tumor Antineoplastic Combined Chemotherapy Protocols Humans AC133 Antigen Enzyme Inhibitors HES1 Lung neoplasms Molecular Biology Glycoproteins A549 cell Receptors Notch Cell Cycle Checkpoints Cell Biology Cell biology P19 cell embryonic structures Neoplastic Stem Cells Amyloid Precursor Protein Secretases Cisplatin Stem cell Peptides Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 444:670-675 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2014.01.164 |
| Popis: | Cancer stem cells (CSCs) are believed to play an important role in tumor growth and recurrence. These cells exhibit self-renewal and proliferation properties. CSCs also exhibit significant drug resistance compared with normal tumor cells. Finding new treatments that target CSCs could significantly enhance the effect of chemotherapy and improve patient survival. Notch signaling is known to regulate the development of the lungs by controlling the cell-fate determination of normal stem cells. In this study, we isolated CSCs from the human lung adenocarcinoma cell line A549. CD133 was used as a stem cell marker for fluorescence-activated cell sorting (FACS). We compared the expression of Notch signaling in both CD133+ and CD133- cells and blocked Notch signaling using the γ-secretase inhibitor DAPT (GSI-IX). The effect of combining GSI and cisplatin (CDDP) was also examined in these two types of cells. We observed that both CD133+ and CD133- cells proliferated at similar rates, but the cells exhibited distinctive differences in cell cycle progression. Few CD133+ cells were observed in the G2/M phase, and there were half as many cells in S phase compared with the CD133- cells. Furthermore, CD133+ cells exhibited significant resistance to chemotherapy when treated with CDDP. The expression of Notch signaling pathway members, such as Notch1, Notch2 and Hes1, was lower in CD133+ cells. GSI slightly inhibited the proliferation of both cell types and exhibited little effect on the cell cycle. The inhibitory effects of DPP on these two types of cells were enhanced when combined with GSI. Interestingly, this effect was especially significant in CD133+ cells, suggesting that Notch pathway blockade may be a useful CSC-targeted therapy in lung cancer. |
| Databáze: | OpenAIRE |
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