【摘要】：目的探討低糖高乳酸微環(huán)境對(duì)表皮生長(zhǎng)因子酪氨酸激酶抑制劑(EGFR-TKI)抑制He La細(xì)胞的影響和可能機(jī)制。方法 He La細(xì)胞在常糖(葡萄糖10 mmol/L)和低糖高乳酸(葡萄糖3 mmol/L+乳酸2.5 mmol/L)環(huán)境下培養(yǎng),并分別給予2.67μmol/L吉非替尼干預(yù)。采用CCK-8法測(cè)定He La細(xì)胞生長(zhǎng)抑制率,流式細(xì)胞術(shù)檢測(cè)細(xì)胞周期,熒光定量RT-PCR檢測(cè)EGFR和m TOR m RNA水平的表達(dá)。結(jié)果與常糖組比較,低糖乳酸組24 h和72 h細(xì)胞抑制率均顯著升高(P0.01),48 h細(xì)胞抑制率略高于常糖組。與吉非替尼陰性組比較,常糖+吉非替尼組和低糖乳酸+吉非替尼組在24、48、72 h三個(gè)時(shí)點(diǎn)細(xì)胞抑制率均顯著上升(P0.01)。與常糖組相比,低糖乳酸組48 h細(xì)胞誘導(dǎo)凋亡率顯著上升(P0.01),低糖乳酸+吉非替尼組細(xì)胞誘導(dǎo)凋亡率較低糖乳酸組顯著降低(P0.01)。與常糖組比較,低糖乳酸組存活細(xì)胞的EGFR和m TOR m RNA表達(dá)水平上調(diào)(P0.05)。常糖+吉非替尼組的EGFR和m TOR m RNA水平均上調(diào)(P0.05)。與低糖乳酸組比較,低糖乳酸+吉非替尼組的EGFR和m TOR m RNA上調(diào)水平有顯著差異(P0.01)。結(jié)論高乳酸低糖環(huán)境下吉非替尼可大幅度上調(diào)存活He La細(xì)胞EGFR和m TOR表達(dá)水平,可能是誘導(dǎo)He La細(xì)胞抵抗EGFR-TKI的機(jī)制。
[Abstract]:Objective to investigate the effect and possible mechanism of low glucose and high lactic acid microenvironment on the inhibition of He La cells by epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). Methods He La cells were cultured in normal glucose (glucose 10 mmol/L) and low glucose high lactic acid (glucose 3 mmol/L lactic acid 2.5 mmol/L) environment and treated with 2.67 渭 mol / L gefitinib, respectively. The growth inhibition rate of He La cells was measured by CCK- 8 assay, the cell cycle was detected by flow cytometry, and the expression of EGFR and m TOR m RNA was detected by fluorescence quantitative RT-PCR. Results compared with normal glucose group, the inhibition rate of cells in low glucose lactic acid group increased significantly at 24 h and 72 h (P 0.01), and the cell inhibition rate at 48 h was slightly higher than that in normal glucose group. Compared with gefitinib negative group, the cell inhibition rate of normal glucose gifetene group and low glucose lactic acid gifitinib group increased significantly at 24 h, 48 h and 72 h (P 0.01), and the cell inhibition rate was significantly increased at 24 h, 48 h and 72 h, respectively (P 0.01). Compared with normal glucose group, the apoptosis rate of cells in low glucose lactic acid group increased significantly at 48 h (P 0.01), and the apoptosis rate in low glucose lactic acid group was significantly lower than that in low glucose lactic acid group (P 0.01). Compared with normal glucose group, the expression of EGFR and m TOR m RNA in survival cells of low glucose lactic acid group was up-regulated (P 0.05). The levels of EGFR and m TOR m RNA in giferinib group were up-regulated (P 0.05). Compared with the low glucose lactic acid group, the up-regulation levels of EGFR and m TOR m RNA in the low glucose lactic acid group were significantly different (P 0.01). Conclusion gefitinib can significantly up-regulate the expression of EGFR and m-TOR in survival He La cells in high lactic acid and low glucose environment, which may be the mechanism of inducing He La cells to resist EGFR-TKI.
【作者單位】： 福建醫(yī)科大學(xué)附屬泉州市第一醫(yī)院;北京中醫(yī)藥大學(xué);廈門大學(xué);
【基金】：泉州市第一醫(yī)院青年科研(2014-QN-24) 泉州市科技計(jì)劃項(xiàng)目(2015241) 國(guó)家面上項(xiàng)目(81672094)
【分類號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前5條

1 孫瑤;;宮頸癌的靶向藥物治療研究進(jìn)展[J];現(xiàn)代中西醫(yī)結(jié)合雜志;2016年12期

2 聶丹;劉玲;夏紀(jì)毅;汪春燕;詹平;毛熙光;;血管生成素樣蛋白4(ANGPTL4)敲低抑制宮頸癌SiHa細(xì)胞增殖并促進(jìn)其凋亡[J];細(xì)胞與分子免疫學(xué)雜志;2016年04期

3 鄭鳳霞;傅芬;蔡勇;葉稱連;;EGFR、蛋白激酶B在宮頸癌中表達(dá)及EGFR胞外區(qū)基因突變的研究[J];現(xiàn)代婦產(chǎn)科進(jìn)展;2015年07期

4 周素英;張品南;潘丹;夏作利;陳艷梅;馮國(guó)飛;郭群;;組織芯片宮頸癌中EGFR的表達(dá)及意義[J];中華中醫(yī)藥學(xué)刊;2013年09期

5 薛琴琴;張菊;俞青苗;金雯;楊梅;劉寧俠;高艷娥;;宮頸癌組織表皮生長(zhǎng)因子受體對(duì)TKI敏感性相關(guān)的基因突變研究[J];西安交通大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2012年05期

【共引文獻(xiàn)】

相關(guān)期刊論文 前8條

1 李蘋;李麗娜;李明珠;呂育純;林麗蓉;;低糖高乳酸環(huán)境下吉非替尼誘導(dǎo)HeLa細(xì)胞EGFR-TKI耐藥的研究[J];中國(guó)婦產(chǎn)科臨床雜志;2017年02期

2 宋紅梅;宋竹梅;鄧疆鵬;桂金川;方向東;吳福道;;奈達(dá)鉑化療聯(lián)合同期放療治療中晚期宮頸癌臨床效果分析[J];中外醫(yī)學(xué)研究;2016年22期

3 王軍;溫達(dá)雄;黃慧敏;溫惠娟;黃秀凡;;EGFR蛋白在宮頸不同病變組織中的表達(dá)及意義[J];深圳中西醫(yī)結(jié)合雜志;2015年11期

4 鄭鳳霞;聶麗菊;孫平風(fēng);傅芬;;宮頸癌中表皮生長(zhǎng)因子受體基因狀態(tài)的研究進(jìn)展[J];中國(guó)婦幼保健;2015年15期

5 李慶云;王霞靈;彭小鵬;徐正富;;宮頸康治療宮頸HPV感染臨床研究[J];遼寧中醫(yī)藥大學(xué)學(xué)報(bào);2015年05期

6 范甜;;中西醫(yī)結(jié)合治療660例子宮肌瘤臨床效果分析[J];大家健康(學(xué)術(shù)版);2014年21期

7 鄧克紅;王晨陽(yáng);王武亮;;西妥昔單抗聯(lián)合奈達(dá)鉑對(duì)宮頸癌Hela細(xì)胞增殖的影響[J];鄭州大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2014年01期

8 劉秀敏;劉亞菲;周俊杰;孟文穎;;淺析米非司酮對(duì)治療婦產(chǎn)科疾病的影響[J];中國(guó)醫(yī)藥導(dǎo)刊;2013年12期

【二級(jí)參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 吳智鴻;趙硯瑾;王永珍;姚鄭林;江發(fā)龍;匡先照;張養(yǎng)軍;李庶心;;帕唑帕尼衍生物的合成與初步的活性評(píng)價(jià)[J];化學(xué)工程師;2015年04期

2 李昭;李R，

本文編號(hào)：2497064