Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT. Expression of LC3II increased in parallel to the increase of the T4 concentration in both A549 and A549/DDP cells and was repressed by overexpression of AKT. The expression levels of PI3-K, PI3-P, AKT, TSC2, mTOR, p70S6K and 4E-BP1 were minimally affected by the wortmannin, perifosine, or rapamycin plus T4 treatments, but their phosphorylated products were greatly affected in A549 lung cancer cells and slightly affected in A549/DDP lung cancer cells. These results indicate that T4 induces autophagy in lung cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway. We further found that T4 decreased expression of MDR1 and improved cisplatin sensitivity of A549/DDP cells. Altogether, these results have meaningful implications for tumor therapy in the future.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. A growing number of studies have shown that long noncoding RNAs (lncRNAs) play an important role in AP progression. Here, we aimed to elucidate the role of Small Nucleolar RNA Host Gene 11(SNHG11) and its underlying molecular mechanisms behind AP progression. The in vivo and in vitro AP cell models were established by retrograde injection of sodium taurocholate and caerulein stimulation into AR42J cells and HPDE6-C7 cells, respectively. A bioinformatics website predicted the relationship between SNHG11, miR-7-5p, and Phospholipase C Beta 1(PLCB1) and validated it with a dual-luciferase reporter assay and an RNA immunoprecipitation (RIP) assay. AR42J cells and HPDE6-C7 cells were transfected with an overexpression of plasmids or shRNA to investigate the effects of the SNHG11/miR-7-5p/PLCB1 axis on cell proliferation and apoptosis, inflammatory cytokine secretion, and acute pancreatitis. Low expression of SNHG11 and PLCB1 and high expression of miR-7-5p were observed in AP pancreatic tissue and AP cell models. SNHG11 overexpression inhibited apoptosis and inflammatory responses induced by caerulein. Simultaneously, we discovered that SNHG11 regulates PLCB1 expression by sponging miR-7-5p. PLCB1 overexpression abrogated inflammatory damage exacerbated by miR-7-5p enrichment. In addition, the SNHG11/miR-7-5p/PLCB1 axis could be involved in caerulein-induced inflammatory injury by participating in the p38MAPK signaling pathway. The overexpressed SNHG11/miR-7-5p/PLCB1 axis can inhibit AP progression by participating in the p38MAPK signaling pathway, thereby providing a potential therapeutic target and therapeutic direction for AP therapy.

Lung cancer is the most malignant form of cancer and has the highest morbidity and mortality worldwide. Due to drug resistance, the current chemotherapy for lung cancer is not effective and has poor therapeutic effects. Tripchlorolide (T4), a natural extract from the plant Tripterygium wilfordii, has powerful immunosuppressive and antitumour effects and may become a potential therapeutic agent for lung cancer. Therefore, this study aimed to investigate the effect of T4 on reducing chemoresistance in lung cancer cells and to explore the mechanism. 1. A549 and A549/DDP cells were separately transfected with AEG-1 overexpression and AEG-1 knockdown plasmids. A549/DDP cells were divided into the A549/DDP empty group, T4 group, and T4 + AEG-1 overexpression group. A CCK-8 assay was used to evaluate the proliferation of cells in each group. RT–qPCR and Western blotting were used to detect the expression of AEG-1 and MDR-1. Expression of AEG-1 in A549 and A549/DDP cells was positively correlated with cisplatin resistance. When the AEG-1 protein was overexpressed in A549 cells, the lethal effect of cisplatin on A549 cells was attenuated (all P < 0.05). After the AEG-1 protein was knocked down in A549/DDP cells, cisplatin was applied. The lethal effect was significantly increased compared to that in the corresponding control cells (all P < 0.05). AEG-1 protein expression gradually decreased with increasing T4 concentration in A549 and A549/DDP cells. Resistance to cisplatin was reduced after the addition of T4 to A549/DDP cells (P < 0.05), and this effect was enhanced after transfection with the AEG-1 knockdown plasmid. T4 plays an important role in increasing the sensitivity of lung cancer cells to cisplatin.