Roflumilast enhances cisplatin‐sensitivity and reverses cisplatin‐resistance of ovarian cancer cells via cAMP/PKA/CREB‐FtMt signalling axis

Abstract

Roflumilast enhanced DDP sensitivity and reversed the DDP resistance of ovarian cancer cells via activation of cAMP/PKA/CREB pathway and upregulation of the downstream FtMt expression, which has great promise in clinical treatment.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

“…As a broad-spectrum chemotherapeutic drug, the application of cisplatin in glioma treatment is still unsatisfactory. Considerable evidence showed that novel chemosensitizers could effectively improve the anticancer effects of cisplatin and reduce the undesirable adverse effects (Zhang et al 2014;Gong et al 2018;Wandee et al 2019;Zhou et al 2019). Recently, researchers have focussed on the synergistic properties of NB that can effectively improve cell permeability, open BBB, and accelerate drug distribution in tumour tissue (Cai et al 2008;Duan et al 2016;Xing et al 2016).…”

“…Cisplatin, a traditional chemotherapeutic drug, has been widely applied in treating human solid malignancies, including nasopharyngeal, oesophageal, and lung carcinoma, ovarian cancer, and glioma (Rocha et al 2015;Gong et al 2018;Okamoto et al 2018). Cisplatin can interact with DNA and activate apoptotic signalling transduction, which is also negatively regulated by prosurvival factors, such as Bcl-2 family members, PI3K/Akt, and various drug efflux pumps (e.g., ABCB1, also named P-gp or MDR1) (Wijdeven et al 2016;Lipinska et al 2017).…”

“…Considering the development of drug resistance, patients have to receive high doses of cisplatin, thereby leading to undesirable side effects (Sprauten et al 2012). Chemo-sensitization is also an effective strategy to overcome drug resistance and reduce adverse effects (Cao et al 2014;Zhang et al 2014;Gong et al 2018). Thus, the development of novel chemosensitizers to enhance the anticancer efficacy of cisplatin-based therapy is important in clinical cancer treatment.…”

GPRC5A facilitates cell proliferation through cell cycle regulation and correlates with bone metastasis in prostate cancer

“…CREB can regulate transcription of various other transcription factors as well as genes that regulate metabolism, the cell cycle and secretion . Therefore, dysfunction of the cAMP‐dependent pathway can contribute to tumor development, tumor progression and also development of anticancer drug resistance . GPRC5A is known to contain a binding site for CREB in the 5′ promotor region.…”

“…37 Therefore, dysfunction of the cAMPdependent pathway can contribute to tumor development, tumor progression and also development of anticancer drug resistance 38 . 39 GPRC5A is known to contain a binding site for CREB in the 5 0 promotor region. Therefore, GPRC5A may form a negative feedback loop in which the phosphorylation of CREB is suppressed.…”