Spindel Eliot R
Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Handb Exp Pharmacol. 2012(208):451-68. doi: 10.1007/978-3-642-23274-9_19.
Many epithelial and endothelial cells express a cholinergic autocrine loop in which acetylcholine acts as a growth factor to stimulate cell growth. Cancers derived from these tissues similarly express a cholinergic autocrine loop and ACh secreted by the cancer or neighboring cells interacts with M3 muscarinic receptors expressed on the cancer cells to stimulate tumor growth. Primary proliferative pathways involve MAPK and Akt activation. The ability of muscarinic agonists to stimulate, and M3 antagonists to inhibit tumor growth has clearly been demonstrated for lung and colon cancer. The ability of muscarinic agonists to stimulate growth has been shown for melanoma, pancreatic, breast, ovarian, prostate and brain cancers, suggesting that M3 antagonists will also inhibit growth of these tumors as well. As yet no clinical trials have proven the efficacy of M3 antagonists as cancer therapeutics, though the widespread clinical use and low toxicity of M3 antagonists support the potential role of these drugs as adjuvants to current cancer therapies.
许多上皮细胞和内皮细胞表达一种胆碱能自分泌环路,其中乙酰胆碱作为生长因子刺激细胞生长。源自这些组织的癌症同样表达胆碱能自分泌环路,癌症或邻近细胞分泌的乙酰胆碱与癌细胞上表达的M3毒蕈碱受体相互作用以刺激肿瘤生长。主要的增殖途径涉及丝裂原活化蛋白激酶(MAPK)和蛋白激酶B(Akt)的激活。毒蕈碱激动剂刺激肿瘤生长以及M3拮抗剂抑制肿瘤生长的能力在肺癌和结肠癌中已得到明确证实。毒蕈碱激动剂刺激黑色素瘤、胰腺癌、乳腺癌、卵巢癌、前列腺癌和脑癌生长的能力也已得到证实,这表明M3拮抗剂也将抑制这些肿瘤的生长。尽管目前尚无临床试验证明M3拮抗剂作为癌症治疗药物的疗效,但M3拮抗剂的广泛临床应用和低毒性支持了这些药物作为当前癌症治疗辅助药物的潜在作用。