Arca subcrenata Polypeptides Inhibit Human Colorectal Cancer HT-29 Cells Growth via Suppression of IGF-1R/Akt/mTOR Signaling and ATP Production
Arca subcrenata Polypeptides Inhibit Human Colorectal Cancer HT-29 Cells Growth via Suppression of IGF-1R/Akt/mTOR Signaling and ATP Production
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Arca subcrenata 多肽通过抑制 IGF-1R/Akt/mTOR 信号传导和 ATP 产生来抑制人结直肠癌 HT-29 细胞生长
DOI：
10.1080/01635581.2019.1625935
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发表时间：
2020-02
影响因子：
2.9
通讯作者：
Yu Rongmin
中科院分区：
文献类型：
--
作者：
Hu Xianjing;Zheng Weiming;Luo Yuanyuan;Ou Xiaozheng;Song Liyan;Zhang Sirui;He Tingsha;Guo Zhongyi;Zhu Jianhua;Shi Hui;Huang Weijuan;Yu Rongmin
毛蚶广泛分布于近海浅海地区，其肉丸具有食、药双重功能，是人们餐桌上的佳品。本研究的目的是研究A.目的：探讨毛齿素（PAS）对人大肠癌HT-29细胞的作用及其机制。结果表明，PAS作用48 h后对HT-29细胞的生长有明显的抑制作用，其IC 50值为117 μg/ml; PAS 63 mg/kg对HT-29细胞裸鼠移植瘤的生长有明显的抑制作用，而对正常结肠细胞和正常结肠粘膜的影响较小。PAS能诱导HT-29细胞凋亡，并使细胞阻滞于G2/M期。其作用机制可能与抑制IGF-1/IGF-1 R信号通路的激活有关，从而导致下游Akt/mTOR通路的失活。免疫荧光检测显示PAS可降低IGF-1 R（Tyr 1165/1166）的磷酸化水平。IGF-1 R激活剂IGF-1可逆转PAS对IGF-1 R磷酸化的抑制作用。PAS在体内外均能显著抑制HT-29细胞ATP的生成。我们的研究结果为A.毛齿下的大肠杆菌具有成为治疗结肠直肠癌的候选者的潜力。
Abstract Arca subcrenata Lischke, widely scattering offshore at neritic regions, is very popular on dining table due to its edible and medical functional meatball. This study aims to investigate the suppression of a polypeptide fraction from A. subcrenata (PAS) on human colorectal cancer HT-29 cells, and its underlying mechanism. The results showed that PAS inhibited the growth of HT-29 cells with an IC50 value of 117 μg/ml after 48 h treatment, and significantly suppressed the tumor growth in nude mice bearing-xenografted HT-29 cells at the dosage of 63 mg/kg, with little influence on normal colon cells and normal colonic mucosa. PAS was then inspiringly found to induce apoptosis and G2/M phase arrest in HT-29 cells. The effect mechanism was involved in the inhibition of IGF-1/IGF-1R signaling activation, which was responsible for inactivating downstream Akt/mTOR pathway. Immunofluorescence assay also showed that PAS could reduce phosphorylation of IGF-1R (Tyr1165/1166). IGF-1, an IGF-1R activator, could reverse the suppression of PAS on IGF-1R phosphorylation. Furthermore, PAS significantly inhibited ATP production of HT-29 cells both in vitro and in vivo. Our results provide positive evidence that A. subcrenata has the potential to be a candidate for the treatment of colorectal cancer.
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影响因子：
3.5
作者：
Xinge Zhao;Xin Li;Qianyao Ren;Jing Tian;Jian Chen
通讯作者：
Xinge Zhao;Xin Li;Qianyao Ren;Jing Tian;Jian Chen
影响因子：
5.4
作者：
Song L;Li T;Yu R;Yan C;Ren S;Zhao Y
通讯作者：
Zhao Y
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2.7
作者：
Yamamoto, Taketsugu;Oshima, Takashi;Imada, Toshio
通讯作者：
Imada, Toshio
DOI：
--
发表时间：
2009
期刊：
West China Journal of Pharmaceutical Sciences
影响因子：
--
作者：
Yao Quan-sheng
通讯作者：
Yao Quan-sheng