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- 2018
β2肾上腺素受体通过HIF-1α调控NNK诱导的胰腺癌细胞进展
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Abstract:
摘要：目的 探讨β2肾上腺素受体在4-甲基亚硝氨基-3-吡啶-1-丁酮(NNK)诱导胰腺癌细胞进展中的具体作用机制。方法 采用NNK干预胰腺癌MIA PaCa-2和BxPC-3细胞，通过HIF-1α-shRNA稳定转染胰腺癌细胞及运用ICI 118551，以NNK组作为对照，Transwell小室侵袭试验检测各组胰腺癌细胞的侵袭能力，Western blot检测HIF-1α、Cyclin D1和VEGF蛋白表达水平。流式细胞技术检测各组细胞周期变化。结果 NNK能够显著上调MIA PaCa-2和BxPC-3细胞HIF-1α水平及促进胰腺癌细胞的增殖及侵袭能力；β2肾上腺素受体抑制剂ICI 118551及sh-HIF-1α能够显著下调NNK所诱导的MIA PaCa-2和BxPC-3细胞HIF-1α水平，以及抑制胰腺癌细胞的增殖及侵袭能力。另外，运用CoCl2上调HIF-1α表达水平后能够逆转ICI 118551对NNK效应的抑制作用，重新上调胰腺癌细胞的侵袭能力。 结论 β2肾上腺素受体通过HIF-1α来介导NNK诱导的胰腺癌细胞增殖及侵袭。
ABSTRACT: Objective To explore the mechanism of β2-adrenogenic receptor mediating the progression of NNK-induced pancreatic cancer cells. Methods Pancreatic cancer cell lines (MIA PaCa-2 and BxPC-3) were incubated with NNK. ShRNA targeting HIF-1α was applied to knockdown HIF-1α expression. ICI 118551 was used to inhibit β2-adrenogenic receptor signaling. Invasion of MIA PaCa-2 and BxPC-3 cells was detected by Transwell assay. The protein expressions of HIF-1α, Cyclin D1 and VEGF were determined by Western blot. Cell cycle was determined by flow cytometric analysis. Results NNK could significantly upregulate HIF-1α expression in MIA PaCa-2 and BxPC-3 cells and increase the invasion and proliferation of pancreatic cancer cells. However, ICI 118551 or sh-HIF-1α could reverse the effect of NNK on MIA PaCa-2 and BxPC-3 cells. Furthermore, when HIF-1α expression was upregulated by CoCl2, the inhibitory effect of ICI 118551 on NNK was reversed, with a prominent increase in pancreatic cancer cell invasion. Conclusion β2-adrenogenic receptor mediates the invasion and proliferation of NNK-induced pancreatic cancer cells through HIF-1α
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