Preclinical ReportsCombinational treatment of gap junction enhancers and paclitaxel attenuates mammary tumor growthShishido, Stephanie; Nguyen, Thu AnneliseAuthor Information Departments of Diagnostic Medicine/Pathobiology, Kansas State University, Manhattan, Kansas, USA Received 29 July 2019 Revised form accepted 21 November 2019 Correspondence to Thu Annelise Nguyen, PhD, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA, Tel: +1 785 532 4429; fax: +1 785 532 4039; e-mail: email@example.com Anti-Cancer Drugs: April 2020 - Volume 31 - Issue 4 - p 353-358 doi: 10.1097/CAD.0000000000000879 Buy Metrics Abstract A class of substituted quinolines (PQs) acts as a gap junction enhancer with the ability to increase the gap junctional intercellular communication in breast cancer cells. This study examined the effect of a combinational treatment of PQs and the antineoplastic drug paclitaxel in a xenograft animal model. Mice were implanted with estradiol-17ß (1.7 mg/pellet) before the injection of 1 × 107 T47D breast cancer cells subcutaneously into the inguinal region of mammary fat pad. Animals were treated intraperitoneally with DMSO (control), paclitaxel (10 mg/kg), PQ (25 mg/kg), or a combinational treatment of paclitaxel and PQ. There was no significant difference between the paclitaxel-treated animals and the control group after seven injections of treatment for 2 weeks. All mice treated with PQ had a significant decrease in mammary tumor growth. The combinational treatment of paclitaxel and PQ1 or PQ7 showed a reduction in tumor growth by 2.3- and 2.2-fold, respectively, compared to paclitaxel alone after seven treatments every 2 days. Molecular analysis indicated a significant increase of gap junction proteins and caspase signaling in PQ and paclitaxel-treated tissues compared to control. Furthermore, there is evidence of an upregulation of Cyclin D1 expression in paclitaxel-treated tumors compared to control, suggesting that the neoplastic cells were highly proliferative and nonresponsive to the paclitaxel alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs via the enhancement of gap junctions with PQs, a specific class of gap junction enhancers. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.