浏览全部资源
扫码关注微信
尿苷三磷酸增加细胞内Ca2+信号诱导自噬抑制胃癌细胞的增殖
Uridine triphosphate inhibits the proliferation of gastric cancer cells through Ca2+-mediated autophagy
- 第三军医大学学报 2019年41卷第8期 页码：763-769
- 作者机构：
400037 重庆，陆军军医大学(第三军医大学)第二附属医院消化内科Department of Gastroenterology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China
- 作者简介：
- 基金信息：
DOI：10.16016/j.1000-5404.201811004
中图分类号： R73-361;R730.23;R735.2收稿：2018-11-04，
纸质出版：2019-04-30
- 稿件说明：
移动端阅览
高楠楠, 万晗星, 董辉, 等. 尿苷三磷酸增加细胞内Ca2+信号诱导自噬抑制胃癌细胞的增殖[J]. 第三军医大学学报, 2019,41(8):763-769.
Nannan GAO, Hanxing WAN, Hui DONG, et al. Uridine triphosphate inhibits the proliferation of gastric cancer cells through Ca2+-mediated autophagy[J]. Journal of Third Military Medical University, 2019, 41(8): 763-769.
高楠楠, 万晗星, 董辉, 等. 尿苷三磷酸增加细胞内Ca2+信号诱导自噬抑制胃癌细胞的增殖[J]. 第三军医大学学报, 2019,41(8):763-769. DOI： 10.16016/j.1000-5404.201811004.
Nannan GAO, Hanxing WAN, Hui DONG, et al. Uridine triphosphate inhibits the proliferation of gastric cancer cells through Ca2+-mediated autophagy[J]. Journal of Third Military Medical University, 2019, 41(8): 763-769. DOI： 10.16016/j.1000-5404.201811004.
摘要
目的
2
观察尿苷三磷酸(uridine triphosphate，UTP)对胃癌细胞增殖的影响，并探讨其分子机制。
方法
2
采用CCK-8实验检测UTP及加入细胞内钙螯合剂BAPTA-AM后对胃癌细胞SGC-7901和AGS增殖能力的影响；集落形成实验检测UTP对胃癌细胞SGC-7901和AGS集落形成能力的影响；细胞内钙测定实验检测UTP对胃癌细胞SGC-7901和AGS内钙信号的影响；Western blot检测UTP及加入BAPTA-AM后对胃癌细胞SGC-7901和AGS LC3Ⅱ/LC3Ⅰ蛋白表达的影响。
结果
2
UTP抑制SGC-7901和AGS胃癌细胞的增殖(
P
<
0.05)及集落形成能力，此增殖能力可被细胞内钙螯合剂BAPTA-AM逆转；钙测定实验显示UTP可触发胃癌细胞SGC-7901和AGS内的Ca
2+
信号；Western blot检测证实UTP可以上调胃癌细胞SGC-7901和AGS LC3Ⅱ/LC3Ⅰ蛋白表达水平，同时能够被BAPTA-AM阻断(
P
<
0.05)。
结论
2
UTP抑制胃癌细胞的增殖，可能与增加胃癌细胞内钙信号，上调LC3Ⅱ/LC3Ⅰ蛋白表达，进而引起自噬有关。
Abstract
Objective
2
To study the effect of uridine triphosphate (UTP) on the proliferation of gastric cancer cells and explore the underlying molecular mechanisms.
Methods
2
The effects of UTP and BAPTA-AM (an intracellular calcium chelator) on the proliferation of gastric cancer cell lines SGC-7901 and AGS were tested using CCK-8 assay. Colony formation assay was used to assess the effect of UTP on the colony-forming ability of gastric cancer cells. The effect of UTP on cyt in the cells was explored with digital Ca
2+
imaging. Western blotting was performed to observe the effect of UTP and BAPTA-AM on the protein expression of LC3Ⅱ/LC3Ⅰ in the cells.
Results
2
UTP significantly inhibited the proliferation and the colony-forming ability of SGC-7901 and AGS cells(
P
<
0.05)
and these inhibitory effects were reversed by BAPTA-AM. Digital Ca
2+
imaging showed that UTP obviously increased cyt in the gastric cancer cells. The results of Western blotting showed that UTP significantly up-regulated the protein expression of LC3Ⅱ/LC3Ⅰ in the cells
and the application of BAPTA-AM obviously blocked the effect of UTP(
P
<
0.05).
Conclusion
2
UTP inhibits the proliferation of gastric cancer cells probably through increasing calcium signaling and up-regulating LC3Ⅱ/LC3Ⅰ
and thus causing autophagy.
关键词
Keywords
references
BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2 018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.
YANG L, ZHENG R S, WANG N, et al . Incidence and mortality of stomach cancer in China, 2014[J ] . Chin J Cancer Res, 2018, 30(3): 291-298. DOI: 10.21147/j.issn.1000-9604.2018.03.01.
JIN H N, EUN S Y, LEE J S, et al . P2Y2 receptor acti-vation by nucleotides released from highly metastatic breast cancer cells increases tumor growth and invasion via crosstalk with endothelial cells[J ] . Breast Cancer Res, 2014, 16(5): R77. DOI: 10.1186/bcr3694.
WHITE N, BURNSTOCK G. P2 receptors and cancer[J]. Trends Pharmacol Sci, 2006, 27(4): 211-217. DOI: 10.1016/j.tips.2006.02.004.
万晗星, 谢睿, 刘菁菁, 等.尿苷三磷酸通过PTEN/Vimentin抑制胃癌细胞的侵袭[J].第三军医大学学报, 2016, 38(6): 550-553. DOI: 10.16016/j.1000-5404.201510120.
WAN H X, XIE R, LIU J J, et al . UTP attenuates migration of gastric cancer cells via PTEN/vimentin[J ] . J Third Mil Med Univ, 2016, 38(6): 550-553. DOI: 10.16016/j.1000-5404.201510120.
SHAPOVALOV G, RITAINE A, SKRYMA R, et al . Role of TRP ion channels in cancer and tumorigenesis[J ] . Semin Immunopathol, 2016, 38(3): 357-369. DOI: 10.1007/s00281-015-0525-1.
LIU X Y, WAN X, KAN H, et al . Hypoxia-induced upregulation of Orai1 drives colon cancer invasiveness and angiogenesis[J ] . Eur J Pharmacol, 2018, 832: 1-10. DOI: 10.1016/j.ejphar.2018.05.008.
LIAO C H, ZHENG K, LI Y, et al . Gypenoside L inhibits autophagic flux and induces cell death in human esophageal cancer cells through endoplasm reticulum stress-mediated Ca 2+ release[J ] . Oncotarget, 2016, 7(30): 47387-47402. DOI: 10.18632/oncotarget.10159.
SOUZA C O, SANTORO G F, FIGLIUOLO V R, et al . Extracellular ATP induces cell death in human intestinal epithelial cells[J ] . Biochim Biophys Acta, 2012, 1820(12): 1867-1878. DOI: 10.1016/j.bbagen.2012.08.013.
CHOI J H, JI Y G, LEE D H. Uridine triphosphate increases proliferation of human cancerous pancreatic duct epithelial cells by activating P2Y2 receptor[J]. Pancreas, 2013, 42(4): 680-686. DOI: 10.1097/MPA.0b013e318271bb4b.
CÁRDENAS C, MILLER R A, SMITH I, et al . Essential regulation of cell bioenergetics by constitutive InsP3 receptor Ca 2+ transfer to mitochondria[J ] . Cell, 2010, 142(2): 270-283. DOI: 10.1016/j.cell.2010.06.007.
GROTEMEIER A, ALERS S, PFISTERER S G, et al . AMPK-independent induction of autophagy by cytosolic Ca 2+ increase[J ] . Cell Signal, 2010, 22(6): 914-925. DOI: 10.1016/j.cellsig.2010.01.015.
JI T R, ZHANG C W, MA L L, et al . TRPC6-mediated Ca 2+ signaling is required for hypoxia-induced autophagy in human podocytes[J ] . Cell Physiol Biochem, 2018, 48(4): 1782-1792. DOI: 10.1159/000492351.
RAH S Y, LEE Y H, KIM U H. NAADP-mediated Ca 2+ signaling promotes autophagy and protects against LPS-induced liver injury[J ] . FASEB J, 2017, 31(7): 3126-3137. DOI: 10.1096/fj.201601290R.
CHOI R C, CHU G K, SIOW N L, et al . Activation of UTP-sensitive P2Y2 receptor induces the expression of cholinergic genes in cultured cortical neurons: A signaling cascade triggered by Ca 2+ mobilization and extracellular regulated kinase phosphorylation[J ] . Mol Pharmacol, 2013, 84(1): 50-61. DOI: 10.1124/mol.112.084160.
RABINOWITZ J D, WHITE E. Autophagy and metabolism[J]. Science, 2010, 330(6009): 1344-1348. DOI: 10.1126/science.1193497.
GEWIRTZ D A. The four faces of autophagy: implications for cancer therapy[J]. Cancer Res, 2014, 74(3): 647-651. DOI: 10.1158/0008-5472.CAN-13-2966.
WHITE E, DIPAOLA R S. The double-edged sword of autophagy modulation in cancer[J]. Clin Cancer Res, 2009, 15(17): 5308-5316. DOI: 10.1158/1078-0432.CCR-07-5023.
GAO Y, QI W W, SUN L B, et al . FOXO3 inhibits human gastric adenocarcinoma (AGS) cell growth by promoting autophagy in an acidic microenvironment[J ] . Cell Physiol Biochem, 2018, 49(1): 335-348. DOI: 10.1159/000492884.
CHEN P P, MA X Y, LIN Q, et al . Kangfuxin promotes apoptosis of gastric cancer cells through activating ER-stress and autophagy[J ] . Mol Med Rep, 2017, 16(6): 9043-9050. DOI: 10.3892/mmr.2017.7716.
0
浏览量
0
下载量
0
CSCD
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
