RESUMO
Background: Platinum-based dual-drug first-line chemotherapy is commonly employed in the treatment of patients with advanced non-small cell lung cancer (NSCLC), although its clinical efficacy is limited. Bevacizumab can antagonize vascular endothelial cell growth factor (VEGF), which inhibit tumor angiogenesis and prevent tumor invasion and development. However, a comprehensive meta-analysis evaluating the effectiveness and safety of combining bevacizumab with platinum-based chemotherapy in advanced NSCLC patients is lacking. Methods: Randomized controlled trials (RCTs) investigating the combination therapy of bevacizumab and platinum-based chemotherapy for treating advanced NSCLC were searched across six databases. Data on objective response rate (ORR), disease control rate (DCR), 1-year survival rate, 2-year survival rate, 3-year survival rate, VEGF levels, and side effects were synthesized. Relative risk degree (RR) along with 95% confidence interval (CI) was used as statistical analysis measures for binary outcomes while continuous variables were analyzed using mean difference (MD) along with 95% CI. Heterogeneity was evaluated by Chi-squared and I2 tests. If there was heterogeneity, subgroup analysis was performed. Sensitivity analysis of the main outcome measures and assessment of publication bias were also performed. Results: According to our screening criteria, a total of Forty-nine RCTs were included, involving data from 4268 patients. The results of this analysis showed that compared with platinum-containing chemotherapy alone, bevacizumab combined with platinum-containing chemotherapy significantly improved ORR (RR [95% CI], 1.53 [1.44, 1.63], p < 0.00001), DCR (RR [95% CI], 1.24 [1.19, 1.29], p < 0.0001), 1-year survival rate (RR [95% CI], 1.34 [1.15, 1.57], p = 0.0003), 2-year survival rate (RR [95% CI], 2.16 [1.35, 3.43], p = 0.001), 3-year survival rate (RR [95% CI], 2.00 [1.21, 3.30], p = 0.007). In addition, bevacizumab with platinum-containing chemotherapy observably decreased the VEGF levels (RR [95% CI], -67.35 [-91.46, -43.25], p < 0.00001). Conclusion: Combination therapy involving bevacizumab demonstrated improved antitumor effects compared to chemotherapy alone in terms of ORR, DCR, 1-year survival rate, 2-year survival rate, 3-year survival rate, and VEGF levels without an increased incidence of adverse reactions. These analyses' results can provide clinicians guidance when selecting appropriate treatments for patients diagnosed with advanced non-small cell lung cancer.
RESUMO
Intermittent fasting as an adjuvant therapy in clinical practice is an emerging treatment modality to target tumor growth by reducing glucose utilization. Berberine, an alkaloid extracted from the traditional Chinese medicine Coptidis Rhizoma, has been shown to be a safe and effective antitumor agent in several cancers. Hence, the purpose of the present study was to investigate the effects of the combination of berberine and low glucose on gastric cancer. Our results showed that the combination of berberine and low glucose effectively inhibited cell viability, promoted apoptosis, and reduced the migration ability of MGC803 cells. In addition, the combination was shown to activate the PP2A/GSK3ß signaling axis, leading to the downregulation of the downstream pro-survival protein MCL-1, which leads to the death of gastric cancer cells. In addition, the inhibitor of GSK3ß partially reversed the effect of this combination on MGC803 cells. In vivo experiments demonstrated that berberine effectively impaired the growth of xenograft tumors, when administered during intermittent fasting (hypoglycemic conditions), and was well tolerated by nude mice without the occurrence of any adverse effects. Based on these results, we conclude that the berberine/low-glucose combination can inhibit the growth of gastric cancer through the PP2A/GSK3ß/MCL-1 signaling pathway. Accordingly, this combination of drugs and lifestyle may become a new type of safe and effective anti-cancer therapy.
