Lappaconitine sulfate (LS) has good solubility and bioavailability. We have previously studied the anti-proliferative activity of LS on colon cancer HT-29 cell, but its anti-proliferative activity and molecular mechanism on human non-small cell lung cancer A549 cells are still unclear. This study was to investigate the effects of LS on proliferation, cell cycle and apoptosis in human non-small cell lung cancer A549 cells, and its possible molecular mechanisms. Cell proliferation activity was measured by Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2′- deoxyuridine (EdU) cell proliferation kit. Cell cycle was detected by propidium iodide (PI) flow cytometry. Apoptosis was detected by Annexin-V-FITC/PI method. Western blot was used to detect cycle and apoptosis-related proteins expression. These results showed that the proliferation activity of LS was significantly decreased in A549 cells, showing a dose- and time-dependent manner (p < 0.05). LS could increase the proportion of G0/G1 phase cells and decrease the proportion of cells in S phase, showing obvious G0/G1 phase arrest. LS significantly inhibited the expression of p-PI3K/PI3K, p-AKT/AKT, Cyclin D1 and Bcl-2 proteins (p < 0.05), and increased the expression of p53, p21, Bax, caspase 3 and caspase 9 (p < 0.05). Moreover, PI3K inhibitor (LY294002) significantly decreased A549 cell viability rate induced by LS, abrogated the activation of p-PI3K/PI3K and p-AKT/AKT in the presence of LS. These results indicated that LS could block A549 cells in the G0/G1 phase, induce apoptosis, and inhibit cell proliferation through the PI3K/AKT signaling pathway.

硫酸拉帕尼汀（LS）具有良好的溶解度和生物利用度。我们先前已经研究了LS对结肠癌HT-29细胞的抗增殖活性，但其对人非小细胞肺癌A549细胞的抗增殖活性和分子机制仍不清楚。本研究旨在探讨LS对人非小细胞肺癌A549细胞增殖，细胞周期和凋亡的影响及其可能的分子机制。细胞增殖活性通过Cell Counting Kit-8（CCK-8）和5-Ethynyl-2'-deoxyuridine（EdU）细胞增殖试剂盒进行测量。细胞周期通过碘化丙啶（PI）流式细胞仪检测。通过膜联蛋白-V-FITC / PI法检测细胞凋亡。Western印迹用于检测周期和凋亡相关蛋白的表达。p＜0.05）。LS可以增加G0 / G1期细胞的比例，减少S期细胞的比例，表现出明显的G0 / G1期停滞。LS显着抑制p-PI3K / PI3K，p-AKT / AKT，Cyclin D1和Bcl-2蛋白的表达（p <0.05），并增加p53，p21，Bax，caspase 3和caspase 9的表达（p < 0.05）。此外，PI3K抑制剂（LY294002）显着降低了LS诱导的A549细胞存活率，消除了在LS存在下p-PI3K / PI3K和p-AKT / AKT的活化。这些结果表明，LS可以通过PI3K / AKT信号通路阻断G0 / G1期的A549细胞，诱导细胞凋亡，并抑制细胞增殖。