Association of lung-intestinal microecology and lung cancer therapy.

In recent years, the incidence of lung cancer is increasing. Lung cancer has become one of the most malignant tumors with the highest incidence in the world, which seriously affects people's health. The most important cause of death of lung cancer is metastasis. Therefore, it is crucial to understand the mechanism of lung cancer progression and metastasis. This review article discusses the physiological functions, pathological states and disorders of the lung and intestine based on the concepts of traditional Chinese medicine (TCM), and analyzes the etiology and mechanisms of lung cancer formation from the perspective of TCM. From the theory of "the exterior and interior of the lung and gastrointestinal tract", the theory of "the lung-intestinal axis" and the progression and metastasis of lung cancer, we proposed e "lung-gut co-treatment" therapy for lung cancer. This study provides ideas for studying the mechanism of lung cancer and the comprehensive alternative treatment for lung cancer patients.

Four Main Active Ingredients Derived from a Traditional Chinese Medicine Guanxin Shutong Capsule Cause Cardioprotection during Myocardial Ischemia Injury Calcium Overload Suppression.

Guanxin Shutong capsule is a traditional Chinese medicine for the treatment of myocardial ischemia (MI). Previous studies have shown that the formula has four main active ingredients (FMAI), protocatechuic acid, cryptotanshinone, borneol, and eugenol. However, the mechanisms of action of these FMAI against MI injury are still not well known. The aim of the present study was to evaluate the protective effects of the FMAI on MI in vitro and in vivo. In vitro, rat neonatal cardiomyocytes were isolated, the cell viability and apoptosis rate were, respectively, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and fluorescence activating cell sorter, and the intracellular calcium concentration ([Ca2+ ]i ) and CaM and CaMKII δ mRNA as well as protein levels were determined. Meanwhile, their downstream targets of RyR2 and PLB were also measured by western blot. In vivo, a rat model of coronary artery ligation was used to evaluate the cardioprotective effects. Infarct sizes of heart tissues and levels of serum biochemical indicators, including creatine kinase, lactate dehydrogenase, superoxide dismutase, and glutamate oxaloacetic transaminase, were measured. The in vitro results showed that the FMAI inhibited cell apoptosis, reduced [Ca2+ ]i , decreased the expression of CaM and CaMKII δ, and increased the expression of RyR2 and PLB. In vivo, the FMAI diminished infract size, reduced creatine kinase, lactate dehydrogenase, and aspartate aminotransferase levels, and enhanced superoxide dismutase activity. In conclusion, our data suggest that the FMAI suppressed calcium overload and exerted its protective effect via its antioxidant, antiinflammatory, and anti-apoptosis activities. Copyright © 2017 John Wiley & Sons, Ltd.

Bafetinib (INNO-406) reverses multidrug resistance by inhibiting the efflux function of ABCB1 and ABCG2 transporters.

ATP-Binding Cassette transporters are involved in the efflux of xenobiotic compounds and are responsible for decreasing drug accumulation in multidrug resistant (MDR) cells. Discovered by structure-based virtual screening algorithms, bafetinib, a Bcr-Abl/Lyn tyrosine kinase inhibitor, was found to have inhibitory effects on both ABCB1- and ABCG2-mediated MDR in this in-vitro investigation. Bafetinib significantly sensitized ABCB1 and ABCG2 overexpressing MDR cells to their anticancer substrates and increased the intracellular accumulation of anticancer drugs, particularly doxorubicin and [(3)H]-paclitaxel in ABCB1 overexpressing cells; mitoxantrone and [(3)H]-mitoxantrone in ABCG2 overexpressing cells, respectively. Bafetinib stimulated ABCB1 ATPase activities while inhibited ABCG2 ATPase activities. There were no significant changes in the expression level or the subcellular distribution of ABCB1 and ABCG2 in the cells exposed to 3 µM of bafetinib. Overall, our study indicated that bafetinib reversed ABCB1- and ABCG2-mediated MDR by blocking the drug efflux function of these transporters. These findings might be useful in developing combination therapy for MDR cancer treatment.

Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin.

An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells than DOX. Animal study revealed that DOX-TNP resulted in greater inhibitory effects on the growth of SW620 and SW620/Ad300 tumors than DOX. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX. But DOX-TNP had no effect on the plasma concentrations of DOX. Furthermore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. Ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment.

bba, a synthetic derivative of 23-hydroxybutulinic acid, reverses multidrug resistance by inhibiting the efflux activity of MRP7 (ABCC10).

Natural products are frequently used for adjuvant chemotherapy in cancer treatment. 23-O-(1,4'-bipiperidine-1-carbonyl) betulinic acid (BBA) is a synthetic derivative of 23-hydroxybutulinic acid (23-HBA), which is a natural pentacyclic triterpene and the major active constituent of the root of Pulsatillachinensis. We previously reported that BBA could reverse P-glycoprotein (P-gp/ABCB1)-mediated multidrug resistance (MDR). In the present study, we investigated whether BBA has the potential to reverse multidrug resistance protein 7 (MRP7/ABCC10)-mediated MDR. We found that BBA concentration-dependently enhanced the sensitivity of MRP7-transfected HEK293 cells to paclitaxel, docetaxel and vinblastine. Accumulation and efflux experiments demonstrated that BBA increased the intracellular accumulation of [(3)H]-paclitaxel by inhibiting the efflux of [(3)H]-paclitaxel from HEK293/MRP7 cells. In addition, immunoblotting and immunofluorescence analyses indicated no significant alteration of MRP7 protein expression and localization in plasma membranes after treatment with BBA. These results demonstrate that BBA reverses MRP7-mediated MDR through blocking the drug efflux function of MRP7 without affecting the intracellular ATP levels. Our findings suggest that BBA has the potential to be used in combination with conventional chemotherapeutic agents to augment the response to chemotherapy.