Cisplatin (DDP) is one of the first‐line chemotherapeutic agents for non‐small cell lung cancer (NSCLC). However, repeated use of cisplatin in clinical practice often induces chemoresistance. The aims of this study were to investigate whether rosmarinic acid (RA) could reverse multidrug resistance (MDR) in NSCLC and to explore the underlying mechanisms. Our data demonstrated that RA significantly inhibited NSCLC cell proliferation and cell colony formation in a dose‐dependent manner, induced G1 phase cell cycle arrest and apoptosis, and increased the sensitivity of cell lines resistant to DDP. Mechanistically, RA inhibited NSCLC cell growth, arrested cell cycle, and induced apoptosis by activating MAPK and inhibiting the expression of P‐gp and MDR1, which correspondingly enhanced p21 and p53 expression. We observed that the growth of xenograft tumors derived from NSCLC cell lines in nude mice was significantly inhibited by combination therapy. We demonstrate that RA is a potentially effective MDR reversal agent for NSCLC, based on downregulation of MDR1 mRNA expression and P‐gp. Together, these results emphasize the putative role of RA as a resistance reversal agent in NSCLC.

Background: Surgical resection of the lesion is the standard primary treatment of gastric cancer. Unfortunately, most patients are already in the advanced stage of the disease when they are diagnosed with gastric cancer. Alternative therapies, such as radiation therapy and chemotherapy, can achieve only very limited benefits. The emergence of cancer drug resistance has always been the major obstacle to the cure of tumors. The main goal of modern cancer pharmacology is to determine the underlying mechanism of anticancer drugs. Objective: Here, we mainly review the latest research results related to the mechanism of chemotherapy resistance in gastric cancer, the application of natural products in overcoming the chemotherapy resistance of gastric cancer, and the new strategies currently being developed to treat tumors based on immunotherapy and gene therapy. Conclusion: The emergence of cancer drug resistance is the main obstacle in achieving alleviation and final cure for gastric cancer. Mixed therapies are considered to be a possible way to overcome chemoresistance. Natural products are the main resource for discovering new drugs specific for treating chemoresistance, and further research is needed to clarify the mechanism of natural product activity in patients.

Background. Hepatocellular carcinoma (HCC) is one of the major malignancies associated with high mortality rates. Chinese herbal medicine (CHM) alone, or in combination with conventional therapies (CT), has been widely used for patients with HCC in China. This study aims to explore how integrative therapy (IT) through the combination of CHM and CT affects the survival of patients with intermediate-advanced HCC. Methods. A retrospective cohort study was performed at the First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Data of consecutive patients diagnosed with intermediate-advanced HCC and a specific traditional Chinese medicine diagnostic pattern between January 2006 and December 2013 were retrieved from the electronic medical record system at the hospital. Patients were divided into 3 groups based on the therapies used, that is, IT, CHM alone, and CT alone, and the survival times of these patients was compared. Results. A total of 328 patients were included in this study. Median follow-up period was 26.4 months (95% confidence interval [CI] = 22.7-38.9). Median overall survival was 11.0 months for IT, 8.6 months for CHM, and 9.4 months for CT groups (P < .001). The adjusted hazard ratio (HR) of death for the IT group was 0.55 (95% CI = 0.38-0.79, P = .001) relative to the CT group and 0.68 (95% CI = 0.52-0.90, P = .007) relative to the CHM group, after adjusting for the factors that impact prognosis. Stratified analysis shows that IT can significantly lower the risk of death, especially for patients with good performance status (PS) and Child-Pugh class A. Conclusions. It was indicated that the integrative approach with combination of CHM and CT might improve survival for patients with intermediate-advanced HCC, especially for patients with good PS and Child-Pugh class A. However, a randomized controlled trial is warranted for a conclusive statement.

Purpose. Many patients with advanced non-small-cell lung cancer (NSCLC) seek help from Chinese herbal medicine (CHM). The purpose of this study was to investigate the survival between CHM and chemotherapy (CT) treatment of patients aged ≥60 years with advanced Epidermal Growth Factor Receptor (EGFR) wild type NSCLC and Karnofsky Performance Status (KPS) ≥ 60. Methods. We extracted individual data of all eligible patients from 1 randomized control trial and 2 cohort studies and performed a pooled analysis. Survival outcomes of patients were compared between CHM group and CT group using Cox regression model stratified for study. Results. A total of 486 patients were included in the study, including 262 patients in the CHM group and 224 patients in the CT group. The median overall survival time was 10.9 (95% confidence intervals [CI]: 8.9-13.0) months in CHM group and 9.8 (95% CI: 8.1-11.5) days in CT group (p=0.592). The adjusted hazard ratio (HR) and 95% CI for CHM compared to CT are 0.98 (0.87, 1.10, p=0.751) in the stratified Cox regression model. Stratified analysis showed a trend that previously treated elderly patients with EGFR wild type advanced NSCLC probably gain greater survival benefit from CHM (adjusted HR:0.83, 95% CI: 0.68-1.01, p=0.063). Conclusions. There might be no significant difference in survival for elderly patients with advanced EGFR wild type NSCLC between the CHM and CT groups in the current study. And previously treated elderly patients with advanced NSCLC probably receive greater benefit from CHM. However, limited by the design and unpreplanned study hypothesis, the results must be confirmed by randomized control trial before making a conclusion.

Background: Chloride intracellular channel 1 (CLIC1) plays an important role in the process of cell epithelial transport, and is also involved in tumor invasion and metastasis. Due to its aberrant expression in cancer, the mechanism of action of CLIC1 in cancer has been carefully studied. In this study, we tried to investigate the relationship between CLIC1 and lung adenocarcinoma (LUAD). Methods: The RNA-sequencing data and clinical information of CLIC1 in lung adenocarcinoma were collected from the the cancer genome altas (TCGA) database and analyzed with R software. Paired t test and Mann–Whitney U test were used to detect differences between LUAD tissue and adjacent normal tissue, and the pROC software package performed reactive oxygen species (ROC) curves to detect cutoff values for CLIC1. The expression of CLIC1 in normal human tissues was extracted from the human protein altas (HPA) database, and analyzed clinical proteomic tumor analysis consortium by using UALCAN programme. The relationship between CLIC1 and LUAD was explored by enrichment analysis using gene oncology and Kyoto encyclopedia of genes and genomes. The tumor immunity estimation resource (TIMER) and integrated repository portal for tumor-immune system interactions (TISIDB) databases were used to analyze the correlation between CLIC1 and LUAD immune cell infiltration. Survival analysis of CLIC1 in LUAD was assessed by the PrognoScan database. Results: Compared with normal tissues, both mRNA (messenger Ribose Nucleic Acid) and protein of CLIC1 were overexpressed in LUAD, which was associated with shorter overall survial (OS). In addition, CLIC1 expression was in connection with some clinical-pathological characteristics like tumor node metatasis stages and lymph node metastases. What’s more, CLIC1 may play a role in the immune infiltration of LUAD. Conclusion: In summary, CLIC1 is up-regulated in LUAD and is associated with tumor metastasis, tumor staging, and OS. It may be regarded as a novel marker for prognostic judgement in LUAD.