The present study investigated and evaluated the correlation between the expression of LACTB and LC3 and the clinical outcomes of patients with advanced gastric cancer treated with oxaliplatin plus S-1 neoadjuvant chemotherapy (NACT). A total of 51 patients with advanced gastric cancer underwent NACT treatment between June 2015 and June 2017. Pathomorphological changes in gastric cancer were analyzed by H&E staining. The expression level and subcellular localization of LACTB and LC3 in paraffin-embedded biopsies were detected by immunohistochemistry and immunofluorescence. The mRNA and protein expression of LACTB were investigated by reverse transcription quantitative polymerase chain reaction and Western blotting, respectively. Statistical analysis was performed to determine the association between the expression of LACTB and LC3 and clinical chemotherapy efficacy of NACT for gastric cancer. Among the 51 patients, 3 (5.88%), 27 (52.94%), 13 (25.49%) and 8 (15.69%) displayed complete remission, partial remission, stable disease and progressive disease, respectively. The rate of decreased LACTB expression was 68.6%, while the rate of increased LC3 expression was 60.8%. Furthermore, there was a significant negative correlation between the expression of LACTB and that of LC3 following NACT (P<0.001). High expression of LC3 (P<0.01) and low expression of LACTB (P<0.01) were associated with a poor response of patients with advanced gastric cancer to NACT. In conclusion, the expression of LACTB and LC3 may serve as a promising novel biomarker for determining the prognosis of patients with advanced gastric cancer receiving NACT, while its potential clinical significance requires further elucidation.
Background. Gastric cancer is one of the most common malignant tumors in the world. Albumin paclitaxel (Nab-PTX) is a novel microtubule inhibitor with albumin as the carrier. Several clinical trials are underway in gastric cancer, but the autophagy mechanism of Nab-PTX on gastric cancer is still unclear. The autophagy and apoptosis effects of Nab-PTX compared with 5-pentafluorouracil (5-Fu) and lobaplatin (LBP) in gastric cancer are also unclear. Objective. This article will compare the effects of Nab-PTX, 5-Fu, LBP, and albumin paclitaxel + 5-pentafluorouracil (Nab-PTX + 5-Fu) on AGS cells from the perspective of autophagy and apoptosis, which is to provide new ideas and experimental evidence for gastric cancer. Method. (1) Experimental groups were control (Ctrl), Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu. (2) CCK-8 assay was used to reflect cell viability and proliferation. (3) The flow cytometry was used to perform the 24-hour apoptosis and cell cycle of each group. (4) Western blot assay was used to investigate autophagy signal proteins LC3I/LC3II, LC3II/LC3I, SQSTM1/p62, Beclin-1, Atg12, Atg5, p-mULK1, p-AMPK, p-mTOR, and apoptosis signal proteins Bax and Bcl-2. Results. Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu inhibited AGS cells' proliferation and arrested the cell cycle. At the same time, each group increased the apoptosis of AGS cells to various degrees (Nab-PTX + 5-Fu > Nab-PTX > 5-Fu > LBP, respectively). The experimental results showed that Nab-PTX and Nab-PTX + 5-Fu promoted autophagy and apoptosis of AGS cells. The comparison of Nab-PTX, 5-Fu, and LBP between groups revealed that 5-Fu inhibited autophagy and the expression of apoptosis protein Bax. In LBP, abnormal activation of autophagy downstream, blocking of autophagy flow, abnormal increase of ATG12, and increased expression of apoptosis protein Bax occurred. Further study found that the autophagy upstream mechanism is different. Conclusion. Nab-PTX, 5-Fu, LBP, and Nab-PTX + 5-Fu can inhibit cell proliferation, promote cell apoptosis, and induce the difference in autophagy expression. The autophagy difference of this antitumor drug may be related to its inducing apoptosis. Meanwhile, Nab-PTX has a better antitumor effect than 5-Fu and LBP in gastric cancer, and the combination of Nab-PTX + 5-Fu has more antitumor advantages.
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