title: Blocking the NOTCH pathway can inhibit the growth of CD133-positive A549 cells and sensitize to chemotherapy.
abstract: 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.
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China.
authors: Juntao
authors: J
authors: Liu
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China.
authors: Zhangfan
authors: Z
authors: Mao
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China.
authors: Jie
authors: J
authors: Huang
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China.
authors: Songping
authors: S
authors: Xie
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China.
authors: Tianshu
authors: T
authors: Liu
authors: Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Hubei, China. Electronic address: 48151660@qq.com.
authors: Zhifu
authors: Z
authors: Mao
mesh_terms: D000071916:AC133 Antigen; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002469:Cell Separation; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000032:analysis; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D051880:Receptors, Notch; D053829:Amyloid Precursor Protein Secretases; D002945:Cisplatin
keywords: CD133; Cancer stem cell; Lung cancer; Notch pathway