In the treatment of lung cancer, the multidrug resistance to chemotherapeutic drugs is one of the reasons of low rates for cure and treatment failure, the combination of chemotherapeutic drugs and traditional Chinese medicine can increase the sensitivity of chemotherapy and reduce its adverse effects. Our previous study has proved that Chinese herbal medicine (CHM) Wenxia Changfu Formula (WCF for short) effectively enhances chemotherapeutic efficacy in lung cancer treatment and reverses multidrug resistance in lung cancer cells in vitro. The present study aims to investigate the effect and mechanism of WCF in reversing cell adhesion-mediated drug resistance of lung cancer by using A549 three-dimensional cell culture and nude mouse model of the A549 cell line with Integrin β1 overexpression. We show that the combination of WCF with DDP can decrease proliferation of lung cancer cells by inducing cell cycle arrest and apoptosis. Moreover, we find that the combination of WCF with DDP suppresses the expression of certain molecules which regulate cell cycle and apoptosis. Mechanistically, we show that the Integrin β1, FAK, PI3K, and AKT protein expressions are suppressed by DDP and even more responses are observed when DDP and WCF are combined, showing WCF treatment enhances the effect of commonly used anticancer drugs. In line with the above findings, our results confirm that WCF reverses cell adhesion-mediated drug resistance of lung cancer via inactivating Integrin β1/PI3K/AKT and apoptosis induction.
According to traditional Chinese medicine, lily bulb and Rehmannia decoction (LBRD) is a specialized formula for the treatment of "lily disease", the symptoms of which resemble the clinical manifestations of major depression. However, the molecular basis of the antidepressant mechanism of LBRD and the quality marker ingredients of LBRD remain unclear. This study aimed to investigate the quality marker ingredients of LBRD and to show the molecular mechanism of its antidepressant activities. In this study, we adopted the chronic unpredicted mild stress paradigm to construct a depression model. High-performance liquid chromatography (HPLC) was used to determine the levels of the main markers in LBRD. The underlying mechanism of LBRD was explored by measuring neurotransmitter and cytokine levels using enzyme-linked immunosorbent assay, and by quantifying differentially expressed gene (DEG) of transcriptome in the medial prefrontal cortex (mPFC) tissue through RNA sequencing. HPLC results showed that the average levels of quality marker ingredients of LBRD (ferulic acid, dioscin, verbascoside and catalpol) were 0.00079%, 0.00039%, 0.7% and 1.6% (w/w), respectively. LBRD intervention significantly attenuated the depressive phenotype compared with that in the depressed group. LBRD treatment altered the enriched DEGs in the signaling pathways of γ-aminobutyric acid (GABA) and glutamate neurotransmitter, synaptic plasticity and axon guidance, circadian rhythm and neural-immunity. GABAergic and glutamatergic synapses as well as brain-derived neurotrophic factor (BDNF)/TrkB-dependent phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin-1 (mTOR1), might be the main
Herbs with hot property such as Radix aconiti lateralis preparata and Rhizoma zingiberis could improve the energy metabolism in rats, through influencing the metabolic process of sugar, lipid, and amino acid. It could also promote the production, storage, and utilization of energy by regulating the gene expression related to metabolism, which may be the main molecular mechanism of warming yang and dispelling cold for the treatment of the cold syndrome according to Chinese medicine theory.
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