Efficacy and Safety of Chinese Herbal Medicine on Treatment of Breast Cancer: A Meta-analysis of Randomized Controlled Trials.

Breast cancer is currently the most common cancer in women, and it accounts for 11.6% of all cancer diagnoses in 2018. Breast cancer patients frequently resort to alternative medicine in addition to conventional Western therapy. This study is to evaluate clinical effectiveness of Chinese herbal medicine (CHM) on breast cancer by conducting meta-analyses on 81 randomized controlled trials (RCTs) with a total of 7215 subjects from eight databases. All RCTs compared patients using Western therapy alone and those using additional CHM therapy to evaluate the difference of primary (tumor response, mean time to progression (mTTP), overall survival (OS) and progression free survival (PFS)) and secondary outcome measures (tumor markers). Results showed that under the RECIST1.1 criteria, 52% patients with additional CHM therapy (67%, under WHO criteria) achieved either a complete response (CR) or a partial response (PR), compared to 38% patients with Western therapy alone (53%, under the WHO criteria). The risk ratio was 1.31 ([Formula: see text] < 0.00001, 95% CI = 1.15-1.50) for patients with CHM plus Western therapy and 1.25 ([Formula: see text] < 0.00001, 95% CI = 1.18-1.98) for those with Western therapy. Moreover, patients with complementary CHM therapy were associated with an mTTP of 2.79 months longer ([Formula: see text] < 0.00001) and an OS of 1.90 months longer ([Formula: see text] < 0.00001); they also had an increase in 3-year PFS ([Formula: see text]= 0.002), 2- ([Formula: see text]= 0.0002) and 5-year ([Formula: see text]= 0.006) OS rates. Therefore, complementary CHM therapy might demonstrate clinical benefits for breast cancer patients in terms of tumor response and survival. Clinical studies with further stratification of tumor stages and intervention types are highly warranted.

Combination of Gentiana rhodantha and Gerbera anandria in the BL02 formula as therapeutics to non-small cell lung carcinoma acting via Rap1/cdc42 signaling: A transcriptomics/ bio-informatics biological validation approach.

BACKGROUND: Non-small cell lung cancer (NSCLC) ranks the most commonly diagnosed and highest mortality-leading cancer worldwide despite a variety of treatment strategies are available. The highly heterogeneous and aggressive property of NSCLC as well as its poor prognosis indicates the need for novel therapeutic targets identification. The objective of this study is to identify potential targets from the adjuvant herbal formula BL02 using a combined approach of high throughput transcriptomics and network pharmacology. METHODS: The quality and stability of BL02 were assessed by UHPLC analysis. The inhibitory effect of BL02 on NSCLC was measured by in vivo orthotopic intrathoracic mouse model and in vitro cellular models. EGFR-mutant HCC827 and wild type A549 cell lines were employed. Transcriptomics analysis was introduced to profile the gene expression of NSCLC cells treated with BL02; Network pharmacology and molecular docking analyses predicted the interaction of compounds and NSCLC targets. Immuno-blotting and pull-down assays verified the putative targets. RESULTS: The UHPLC analysis revealed that BL02 was relatively stable between batches of production and for 24 months of storage. Orally administration of BL02 was safe and effective to inhibit pulmonary NSCLC growth in mice implanted with A549 and HCC827-generated tumors. BL02 exhibited relatively low cytotoxicity to NSCLC cells in vitro, but potently suppressed NSCLC cell motility. The transcriptomic analysis illustrated that EGFR and cellular adhesion-related signaling is involved in BL02 action. Further bioinformatics analysis validated BL02 activity is mediated by cdc42-regulated signaling. BL02 depolymerized the actin cytoskeleton through suppressing cdc42 and deactivating its upstream molecule Rap1. These effects may be primarily mediated by the direct binding of 5-methylcoumarin-4-cellobioside and mangiferin from BL02 to Rap1 protein. CONCLUSION: Our study proposes an integration model of experimental, transcriptomic and bioinformatics analyses in the identification of novel therapeutic target of NSCLC from an adjuvant herbal formula BL02. Our findings revealed that inhibition of Rap1/cdc42 signaling by active compounds 5-methylcoumarin-4-cellobioside and mangiferin from BL02 might be potentially effective therapy for NSCLC.