Drug resistance and tumor recurrence are major obstacles in treating lung cancer patients. Accumulating evidence considers lung cancer stem cells (CSCs) as the major contributor to these clinical ...challenges. Agents that can target lung CSCs could potentially provide a more effective treatment than traditional chemotherapy. Here, we utilized the side-population (SP) method to isolate lung CSCs from A549 and PC-9 cell lines. Subsequently, a high throughput platform, connectivity maps (CMAPs), was used to identify potential anti-CSC agents. An antibiotic, antimycin A (AMA), was identified as a top candidate. SP A549 cells exhibited an elevated stemness profile, including Nanog, β-catenin, Sox2, and CD133, and increased self-renewal ability. AMA treatment was found to suppress β-catenin signaling components and tumor sphere formation. Furthermore, AMA treatment decreased the proliferation of gefitinib-resistant PC-9/GR cells and percentage of SP population. AMA demonstrated synergistic suppression of PC-9/GR cell viability when combined with gefitinib. Finally, AMA treatment suppressed tumorigenesis in mice inoculated with A549 SP cells. Collectively, we have identified AMA using CMAP as a novel antilung CSC agent, which acts to downregulate β-catenin signaling. The combination of AMA and targeted therapeutic agents could be considered for overcoming drug resistance and relapse in lung cancer patients.
碩士
國立臺灣大學
預防醫學研究所
96
Objective As the high incident rate of cancer and prevalence of traditional Chinese medicine (TCM) utilization in Taiwan, this study aimed to develop a conceptual framework of ...the TCM seeking behavior of Taiwanese adolescents with cancer.
Methods Ten adolescents (four males and six females) with cancer at all stages of the illness were interviewed by snowball sampling. Data were collected through in-depth interview by semi-structure guideline and observations, medical chart reviews, and researcher’s reflexive journals. As the data were received and transcribed, editing and immersion/ crystallization were used to represent constructs of the adolescents with cancer.
Results These multifaceted, naturalistic contextures were elicited by TCM out-patient department visiting in clinical status. Five distinct subcategories of the TCM seeking behavior reported by interviewees were emerged. The cancer impact included the mind-body impact after diagnosis, the adverse effect impact of treatment, fami
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