Gap Junction Enhancer Increases Efficacy of Cisplatin to Attenuate Mammary Tumor Growth
نویسندگان
چکیده
Cisplatin treatment has an overall 19% response rate in animal models with malignant tumors. Increasing gap junction activity in tumor cells provides the targets to enhance antineoplastic therapies. Previously, a new class of substituted quinolines (PQs) acts as gap junction enhancer, ability to increase the gap junctional intercellular communication, in breast cancer cells. We examined the effect of combinational treatment of PQs and antineoplastic drugs in an animal model, showing an increase in efficacy of antineoplastic drugs via the enhancement of gap junctions. 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), cisplatin (3.5 mg/kg), PQ (25 mg/kg), or a combining treatment of cisplatin and PQ. Cisplatin alone decreased mammary tumor growth by 85% while combinational treatment of cisplatin and PQ1 or PQ7 showed an additional reduction of 77% and 22% of tumor growth after 7 treatments at every 2 days, respectively. Histological results showed a significant increase of gap junction proteins, Cx43 and Cx26, in PQ-treated tissues compared to control or cisplatin. Furthermore, evidence of highly stained caspase 3 in tumors of combinational treatment (PQ and cisplatin) was seen compared to cisplatin alone. We have showed for the first time an increase in the efficacy of antineoplastic drugs through a combinational treatment with PQs, a specific class of gap junction enhancers.
منابع مشابه
Bioavailability and Efficacy of a Gap Junction Enhancer (PQ7) in a Mouse Mammary Tumor Model
The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the norm...
متن کاملGap Junction Enhancer Potentiates Cytotoxicity of Cisplatin in Breast Cancer Cells.
Cisplatin is one of the most widely used anti-cancer drugs due to its ability to damage DNA and induce apoptosis. However, increasing reports of side effects and drug resistance indicate the limitation of cisplatin in cancer therapeutics. Recent studies showed that inhibition of gap junctions diminishes the cytotoxic effect and contributes to drug resistance. Therefore, identification of molecu...
متن کاملاثر هم افزایی مهاری لاکتوباسیلوس رامنوسوس و داروی سیسپلاتین روی میزان تکثیر سلولهای توموری موشهای BALB/C مبتلا به سرطان پستان
Introduction: The probiotic strains of Lactic Acid Bacillus (LAB) not only affect gastrointestinal tract microflora and stimulate local immune system of this tract but also modify and stimulate systemic immunity by influence on lymph nodes and spleen. Several studies have shown the anti-tumor effect of these kinds of bacteria. This study was designed to assess the probiotic effects of lactobaci...
متن کاملConnexin's Connection in Breast Cancer Growth and Progression
Gap junctions are cell-to-cell junctions that are located in the basolateral surface of two adjoining cells. A gap junction channel is composed of a family of proteins called connexins. Gap junction channels maintain intercellular communication between two cells through the exchange of ions, small metabolites, and electrical signals. Gap junction channels or connexins are widespread in terms of...
متن کاملRole of gap-junctional communication in breast cancer progression and chemoprevention.
Although the etiology of breast cancer is varied, it is likely that the modulation of oncogene and tumor suppressor gene expression may play an important role in mammary tumorigenesis. Consistent with this possibility is the finding of gene amplification or the enhanced expression of various oncogenes in primary human breast tumors and breast tumor cell lines (Callahan 1987, Callahan and Campbe...
متن کامل