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Objective: To evaluate the objectivity and comprehensiveness of Response Evaluation Criteria of Traditional Chinese Medicine for Solid Tumor (Draft, REC-TCM-ST) in application of Chinese medicine therapeutic effect in patients with advanced non-small cell lung cancer (NSCLC). Methods: A retrospective clinical research was used in 104 NSCLC patients in stages of III-IV, 53 cases were in Chinese medicine (CM) group and 51 cases were in Western medicine (WM) group. The therapeutic effect of the two groups was evaluated with both REC-TCM-ST and Response Evaluation Criteria in Solid Tumor (RECIST). Kaplan-Meier method was used to analyze the survival time. Kappa test method was used to test the consistency of the two kinds of evaluation results. Results: According to REC-TCM-ST, the effective rate on relieving tumor mass in the CM group was significantly lower than that in the WM group ( P<0.05), but there was no significant difference in tumor-mass stable rate ( P>0.05); the symptom of weakness in the CM group was improved significantly, indicating better therapeutic effect than that in the WM group ( P<0.01). Karnofsky score in the CM group was significantly better than that in the WM group ( P<0.01). In terms of survival conditions, the median survival time and the survival rate of 6 months, 1 year and 2 years of the CM group were higher than the WM group. The total effective rate was 9.62%, and the total stable rate was 72.12% for 104 cases according to RECIST; while the total effective rate was 34.62%, and the total stable rate was 84.62% according to REC-TCM-ST, thus there were significant differences between the results of the two criteria ( P<0.01), and there was also some consistency between them, but not satisfactory. Conclusions: REC-TCM-ST was used to evaluate the therapeutic effect of CM in the treatment of advanced NSCLC, which shows that its evaluation results can better reflect the advantages and disadvantages of CM, and the effectiveness of CM is more objective and comprehensive than RECIST, so REC-TCM-ST is worthy of further improvement and clinical expansion. [ABSTRACT FROM AUTHOR]

Background: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4–17, 2014; Kim and Bae, Curr Opin Hematol 25:52–59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. Methods: Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a−/− mouse model (Spicer etal., J Biol Chem 275:21555–21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4a−/−mice. Results: In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a−/− mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). Conclusions: Conclusively, WPL could ameliorate GPLs in Atp4a−/− mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The β-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of β-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that β-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, β-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, β-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that β-Asarone inhibits Wnt/β-catenin signaling. Rescuing the activation of Wnt/β-catenin signaling overcomes β-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of β-Asarone in lung cancer, demonstrates that the inhibition of Wnt/β-catenin signaling could be critical for β-Asarone-induced anticancer effects. Our study thus suggests a potential application of β-Asarone as an anticancer agent in the clinical treatment of lung cancer. [ABSTRACT FROM AUTHOR]

The Chinese herbal prescription Yi-Fei San-Jie pill (YFSJ) has been used for adjuvant treatment in patients with lung cancer for a long time. Reports have indicated that the combination of gefitinib (Gef) with YFSJ inhibits the proliferation of EGFR-TKI-resistant cell lines by enhancing cellular apoptosis and autophagy in non-small cell lung cancer (NSCLC). However, the molecular mechanisms underlying the effect of YFSJ on EGFR-TKI resistance and related metabolic pathways remain to be explored. In our report, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), metabolomics, network pharmacology, bioinformatics, and biological analysis methods were used to investigate the mechanism. The UPLC-MS/MS data identified 42 active compounds of YFSJ extracts. YFSJ extracts can enhance the antitumor efficacy of Gef without hepatic and renal toxicity in vivo. The analysis of the metabolomics pathway enrichment revealed that YFSJ mainly affected the tyrosine metabolism pathway in rat models. Moreover, YFSJ has been shown to reverse Gef resistance and improve the effects of Gef on the cellular viability, migration capacity, and cell cycle arrest of NSCLC cell lines with EGFR mutations. The results of network pharmacology and molecular docking analyses revealed that tyrosine metabolism-related active compounds of YFSJ affect EGFR-TKIs resistance in NSCLC by targeting cell cycle and the MET/EGFR signaling pathway; these findings were validated by western blotting and immunohistochemistry. YFSJ inhibits NSCLC by inducing cell cycle arrest in the G1/S phase to suppress tumor growth, cell viability, and cell migration through synergistic effects with Gef via the tyrosine metabolic pathway and the EGFR/MET signaling pathway. To summarize, the findings of the current study indicate that YFSJ is a prospective complementary treatment for Gef-resistant NSCLC. [Display omitted] • The mechanism of Yi-Fei San-Jie pill in reducing epidermal growth factor receptor tyrosine kinase inhibitors resistance could be via its tyrosine metabolism-related antitumor compounds that regulate the MET/EGFR/CDK2 pathway involved in tyrosine metabolism, tumor growth inhibition, and cell cycle arrest in non–small cell lung cancer. • Various cyclins and cyclin-dependent kinases, including CDK2 and CDK4, regulate the cell cycle and the sensitivity to epidermal growth factor receptor tyrosine kinase inhibitors in cancer cells. • EGFR signaling is involved in cell cycle regulation and cell proliferation via the activation of cyclin-dependent kinases, such as CDK2 and CDK4. • Resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non–small cell lung cancer is associated with upregulation of MET signaling. [ABSTRACT FROM AUTHOR]