Panx1 Promotes Cisplatin-induced Apoptosis of A549 Cells by Regulating ATP/IP3 Pathway / 肿瘤防治研究

Objective To observe the regulation of Panx1 on ATP/IP3 signaling pathway and its mechanism during cisplatin-induced apoptosis of lung adenocarcinoma cells. Methods Human lung adenocarcinoma cell line A549 was used as the research object and carbenoxolone (CBX) was used as a drug interference tool. A549 cells were divided into normal control group, the CBX group, the cisplatin (DDP) group and the CBX+DDP group. MTT assay and Annexin V/PI assay were used to detect the survival and apoptosis rates of A549 cells. The relative concentrations of extracellular adenosine triphosphate (ATP) and intracellular inositol triphosphate (IP3) were measured by Chemiluminescence and ELISA. Results Compared with DDP group, the cell survival rate of CBX+DDP group increased, while the early and late apoptotic rates and the release concentration of extracellular ATP and intracellular IP3 decreased (all P < 0.01). Conclusion Panx1 can increase the sensitivity of lung adenocarcinoma cells to cisplatin by regulating the ATP/IP3 signaling pathway.

Mechanism of Chuanxiong Rhizoma intervention on central sensitization of Panx1-Src-NMDAR-2B signaling pathway in neuropathic pain model rats / 中国中药杂志

Excitatory toxicity(ET) is an important factor of neuropathic pain(NPP) induced by central sensitization(CS), and the association of pannexin-1(Panx1)-Src-N-methyl-D-aspartate receptor subunit 2 B(NMDAR-2 B) is an important new pathway for ET to initiate CS. The present study confirmed whether the central analgesic effect of Chuanxiong Rhizoma extract(CRE) was achieved through the synchronous regulation of the brain and spinal pathways of Panx1-Src-NMDAR-2 B. In this study, dynamic and simulta-neo-us microdialysis of the brain and spinal cord in vivo combined with behavioristics, high performance liquid chromatography(HPLC)-fluorescence detection, microdialysis analysis(ISCUS~(flex)), ultrasensitive multifactorial electrochemiluminescence immunoassay, ELISA, and Western blot was employed to investigate the protein expression of NMDAR-2 B, Src, and Panx1, extracellular excitatory amino acids, cytokines, energy metabolites, and substance P in spinal dorsal horn(SDH) and anterior cingulate cortex(ACC) after CRE intervention with the rat model of spared sciatic nerve injury(SNI) as the experimental tool. Compared with the sham group, the SNI group exhibited diminished mechanical withdrawal threshold(MWT)(P<0.01), increased cold spray scores(P<0.01), glutamate(Glu), D-serine(D-Ser), and glycine(Gly) in extracellular fluids of ACC, and Glu, D-Ser, interleukin-1β(IL-1β), and lactic acid(Lac) in extracellular fluids of SDH(P<0.05), dwindled tumor necrosis factor(TNF-α)(P<0.05), and elevated protein levels of NMDAR-2 B, Src, and Panx1 in ACC(P<0.05). Compared with the SNI model rats, high-and medium-dose CRE(CRE-H/M) could potentiate the analgesic activity as revealed by the MWT test(P<0.05) and CRE-M enabled the decrease in cold spray scores(P<0.05). CRE-H/M could inhibit the levels of Glu, D-Ser and Gly in the extracellular fluids of ACC(P<0.05), and the levels of Glu in the extracellular fluids of SDH(P<0.05) in SNI rats. CRE-M significantly increased the levels of glucose(Gluc), Lac, interferon-gamma(IFN-γ), keratinocyte chemoattractant/human growth-regulated oncogenes(KC/GRO), and IL-4 in extracellular fluids of SDH in SNI rats(P<0.05). CRE-H/M/L could also inhibit the levels of NMDAR-2 B, Src and Panx1 in ACC and SDH in SNI rats(P<0.05). The central analgesic effect of CRE is presumedly related to the inhibited release of excitatory amino acid transmitters(Glu, D-Ser and Gly) in ACC and SDH of SNI rats, decreased protein expression of NMDAR-2 B, Src and Panx1 in the two regions, and the regulation of the Panx1-Src-NMDAR-2 B pathway in the spinal cord and brain. The above findings partially clarified the scientific basis of clinical analgesic effect of Chuanxiong Rhizoma.

Research progress of P2X7 receptors involved in pain regulation / 中国药理学通报

The ATP-gated ionotropic P2X7 receptor has been widely concerned in recent years. Upon activation by ATP and its derivatives, P2X7 receptor induces a series of responses such as activation of PANX1 and release of IL-lg. Elucidation of the role and mechanism of P2X7 receptor in pain would provide ideas for the development of new and effective analgesic drugs. This review discusses the recent progress of P2X7 receptor in inflammatory pain, neuropathic pain, cancer pain, and morphine tol-erance , and summarizes the possible mechanism of P2X7 receptor involved in the modulation of pain.