高糖对人乳腺癌细胞体外侵袭能力的影响

Effects of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435

目的探讨高糖对人乳腺癌细胞体外侵袭能力的影响及其可能的作用机制。方法以人乳腺癌MDA-MB-435细胞为研究对象，实验分为低葡萄糖组[葡萄糖浓度（Glu）5．5mmol／L组]、高葡萄糖组（Glu11mmol／L组，Glu25mmol／L组）。干预24h后，采用Transwell侵袭试验检测乳腺癌细胞侵袭能力的变化；RT-PCR法检测乳腺癌细胞基质金属蛋白酶（MMP）．9、MMP-2及上皮型钙黏蛋白（E-cadherin）mRNA的表达；Western印迹法检测乳腺癌细胞MMP-9、MMP-2及E．cadherin蛋白的表达。结果Glu5．5mmol／L组、Glu11mmol／L组、Glu25mmol／L组的穿膜细胞数分别为（504-5）、（65±6）、（774-3）个，Glu11mmol／L组及Glu25mmol／L组的乳腺癌MDA—MB-435细胞侵袭能力均高于Glu5．5mmol／L组（P〈0．05）；Glu11mmol／L组及Glu25mmol／L组MDA—MB-435细胞MMP-9和MMP-2蛋白的表达均显著高于Glu5．5mmol／L组（P〈0．05）；Glu11mmol／L组及Glu25mmol／L组E．cadherinmRNA及蛋白的表达均显著低于Glu5．5mmol／L组（P〈0．05）。结论高糖能够通过上调MMP-9和MMP-2的表达、下调E．cadherin的表达从而促进乳腺癌细胞的远处侵袭能力。

Objective To explore the effects and underlying mechanisms of high glucose on in vitro invasiveness of human breast cancer cell line MDA-MB-435. Methods The invasiveness of MDA-MB-435 was determined by Matrigel-coated transwell chambers. Reverse transcription-polymerase chain reaction （RT-PCR） and Western blot were employed to analyze the cellular expression of matrix metalloproteinase-9/ matrix metalloproteiuase-2/E-cadherin （MMP-9/MMP-2/E-cadherin） gene/protein. Results The invasive breast cancer cell numbers of each group （ Glu 5.5, 11 and 25 mmol/L） were 50 ＋ 5, 65 ＋ 6 and 77 ＋ 3 respectively. Cellular invasion was dramatically enhanced in the Glu 11 and 25 mmol/L group compared with the 5.5 mmol/L group. The MMP-9/MMP-2 protein expression increased significantly in the Glu 11 and 25 mmol/L groups compared with 5.5 mmol/L group while high glucose （ Glu 11 and 25 mmol/L group） down- regulated significantly the E-cadherin mRNA/protein expression. Conclusion High glucose can promote the in vitro invasiveness of human breast cancer cells through the altered expression of MMP-9/MMP-2/E- cadherin.