| You Zou,Xiaolan Li,Deding Tao,Junbo HU,Jianping Gong. Epidermal growth factor enhances chemosensitivity of colon cancer by inducing cancer stem cells to enter the cell cycle. Oncol Transl Med, 2017, 3: 86-90. |
| 表皮生长因子通过诱导结肠癌干细胞进入细胞周期而增强肿瘤化疗敏感性 |
| Epidermal growth factor enhances chemosensitivity of colon cancer by inducing cancer stem cells to enter the cell cycle |
| Received:April 30, 2015 Revised:April 03, 2017 |
| DOI：10.1007/s10330-015-0093-3 |
| 中文关键词: 化疗敏感性；肿瘤干细胞；细胞周期 |
| 英文关键词: chemosensitivity; tumor stem cell; cell cycle |
| 基金项目: |
| Author Name | Affiliation | E-mail | | You Zou | Department of General Surgery,Tongji Hospital,Tongji Medical College in Huazhong University of Science and Technology | melonlan@163.com | | Xiaolan Li | Department of General Surgery,Tongji Hospital,Tongji Medical College in Huazhong University of Science and Technology | yzou2003@163.com | | Deding Tao | Department of General Surgery,Tongji Hospital,Tongji Medical College in Huazhong University of Science and Technology | 63678351@qq.com | | Junbo HU | Department of General Surgery,Tongji Hospital,Tongji Medical College in Huazhong University of Science and Technology | 674307118@qq.com | | Jianping Gong* | Department of General Surgery,Tongji Hospital,Tongji Medical College in Huazhong University of Science and Technology | 674307119@qq.com |
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| 中文摘要: |
| 目的：本研究旨在探讨通过表皮生长因子诱导结肠癌干细胞进入细胞周期，能否增强肿瘤的化疗敏感性。方法：体外实验中，培养的HCT116结肠癌细胞给予生长因子（EGF）刺激使其进入细胞周期。在给予生长因子刺激前后，分别用流式细胞仪分选出其中的CD133+的细胞。对这两组CD133+的细胞，分别用流式细胞术检测其Ki-67的表达率，细胞周期分布比例，加入化疗药物5-Fu诱导后的细胞凋亡率等相关指标。体内实验中，通过将HCT116细胞接种裸鼠皮下，建立移植瘤模型。将裸鼠分为两组，即5-Fu化疗组和5-Fu+EGF联合化疗组。通过测量记录移植瘤的生长情况，进而分析比较细胞周期诱导的联合化疗法的疗效。结果：(1)EGF刺激后，CD133+ HCT116细胞与没经过EGF刺激的CD133+ HCT116细胞相比，其Ki67的表达率及S-G2 / M期的比例明显升高，提示更多的肿瘤干细胞进入细胞周期和增殖状态。（2）EGF刺激后，CD133+ HCT116细胞与没经过EGF刺激的CD133+ HCT116细胞相比，在化疗药物5-Fu诱导下，表现出更高的细胞凋亡率，提示化疗敏感性增加。（3）动物实验表明，裸鼠移植瘤模型中，EGF 和 5-Fu联合化疗组，与单用5-Fu化疗组相比，肿瘤的体积更小。结论：表皮生长因子EGF能增强结肠癌细胞对化疗药物的敏感性，原因与其诱导肿瘤干细胞进入细胞周期有关。 |
| 英文摘要: |
| Objective The aim of the study was to investigate whether colon cancer stem cells induced by epidermal
growth factor (EGF) to enter the cell cycle enhanced the chemosensitivity of colon cancer.
Methods In vitro, EGF was used to stimulate the entry of human colon cancer HCT116 cells into the cell
cycle. Before and after treatment with EGF, CD133 HCT116 cells were collected and flow cytometry was
conducted to determine the apoptosis rate based on the 5-Fu and Ki-67 expression rates. The cell cycle
distribution of the two groups was also determined. In vivo, a subcutaneous xenograft model of HCT116
human colon cancer cell lines in nude mice was established. The nude mice were divided into two groups
and treated with EGF and 5-Fu, respectively. Differences in the growth of implanted tumors revealed the
efficiency of cycle-induction combined chemotherapy.
Results (1) After EGF stimulation, the S-G2/M proportion of CD133 HCT116 cells and Ki67 expression
were increased, indicating that more cancer stem cells entered the cell cycle and promoted proliferation; (2)
After EGF stimulation, CD133 HCT116 cells showed a higher apoptosis rate induced by 5-Fu. (3) Animal
experiments showed that the group subjected to combined treatment with EGF and 5-Fu had smaller tumor
sizes compared to the group treated with 5-Fu alone.
Conclusion EGF enhanced tumor sensitivity to chemotherapeutic drugs, likely by promoting tumor stem
cells to enter the cell cycle. |
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