虎杖提取物白藜芦醇基于miR-506调控SPHK1/S1P /S1PR3通路抑制肺癌侵袭和转移的研究

Traditional Chinese medicine and its extract have unique advantages in the prevention and treatment of lung cancer. Resveratrol extracted from polygonum cuspidatum has been hailed as another green anticancer drug following paclitaxel and the molecular mechanism of resveratrol treating lung cancer is a research hotspot .MiR-506 is a tumor suppressor gene. SPHK1/S1P/ S1PR3 pathway can regulate the growth, invasion and metastasis of tumor cells.Our previous studies have shown that SPHK1 is one of the targets of miR-506, which can inhibit the proliferation and invasion of human lung adenocarcinoma cells through the action of miR-506 on SPHK1.In this study, lentiviral vector will be used to transfect miR-506 gene into human lung cancer cell line A549 and miR-506 transgenic mouse model will be established in order to study the effect of miR-506 on SPHK1/S1P/S1PR3 pathway in A549 cells and mouse lung cancer models and the action of resveratrol on them, make clear whether miR-506 can regulate the SPHK1/S1P/S1PR3 pathway in lung cancer and whether resveratrol can inhibit the growth, invasion and metastasis of lung cancer based on miR-506 regulating SPHK1/S1P/S1PR3 pathway, reveal the new target of resveratrol in the prevention and treatment of lung cancer, and provide a more effective theoretical basis for its clinical application.

中药及其提取物在预防及治疗肺癌方面有着独特的优势 ，虎杖提取物白藜芦醇被喻为继紫杉醇之后的又一绿色抗癌药物，其治疗肺癌的分子机理是目前研究的热点。miR-506是抑癌基因，SPHK1/S1P/ S1PR3通路能调控肿瘤细胞的生长、侵袭和转移。我们前期研究表明SPHK1是miR-506的靶点之一，通过作用于SPHK1，miR-506上调可以抑制人肺腺癌细胞的增殖与侵袭。本课题将应用慢病毒转染miR-506沉默基因至人肺癌细胞A549及miR-506转基因小鼠模型，研究miR-506对SPHK1/S1P/S1PR3通路的影响及白藜芦醇对两者的作用，明确在肺癌中miR-506能否调控SPHK1/S1P/S1PR3通路以及白藜芦醇是否可以基于miR-506调控SPHK1/S1P/S1PR3通路抑制肺癌生长、侵袭和转移，揭示白藜芦醇防治肺癌的新靶点，为其临床应用提供更有力的理论依据。

中药及其提取物在预防及治疗肺癌方面有着独特的优势，虎杖提取物白藜芦醇被喻为继紫杉醇之后的又一绿色抗癌药物，其治疗肺癌的分子机理是目前研究的热点。miR-506是抑癌基因，SPHK1/S1P/S1PR3通路能调控肿瘤细胞的生长、侵袭和转移。我们前期研究表明SPHK1是miR-506的靶点之一，通过作用于SPHK1，miR-506上调可以抑制人肺腺癌细胞的增殖与侵袭。本课题将应用慢病毒转染miR-506沉默基因至人肺癌细胞A549及miR-506转基因小鼠模型，研究miR-506对SPHK1/S1P/S1PR3通路的影响及白藜芦醇对两者的作用，明确在肺癌中miR-506能否调控SPHK1/S1P/S1PR3通路以及白藜芦醇是否可以基于miR-506调控SPHK1/S1P/S1PR3通路抑制肺癌生长、侵袭和转移，揭示白藜芦醇防治肺癌的新靶点，为其临床应用提供更有力的理论依据。本研究表明：①白藜芦醇可以通过上调人肺腺癌A549细胞中miR-506的表达从而抑制SPHK1/S1P/S1PR3 信号通路进而抑制A549细胞的增值、侵袭以及促进A549细胞的凋亡。②miR-506转基因小鼠实验表明miR-506可以抑制肺癌瘤体的生长。③MiR-506通过调控TULP3的表达，可抑制非小细胞肺癌细胞的进展。TULP3可能是miR-506调控肺癌过程的潜在直接或间接靶点。