J Cancer 2019; 10(17):4114-4122. doi:10.7150/jca.30690 This issue
1. Department of Gynecology & Obstetrics, China-Japan Friendship Hospital, Beijing, China, 100029.
2. Department of Pathology, Oriental Hospital of Beijing University of Chinese Medicine, Beijing, China, 100078.
3. China-Japan Friendship School of Clinical Medicine, Peking University, Beijing, China, 100029.
4. Department of Pathology, School of Basic Medical Sciences, Beijing University of Chinese Medicine, Beijing, China, 100029.
5. Department of Biochemistry & Molecular Biology, Institute of Clinical Medical Science, China-Japan Friendship Hospital, Beijing , China, 100029.
Curcumin, as a high effect and low toxicity anti-cancer drug and photosensitiser, has synergistic and complementary effects with photodynamic therapy (PDT). However, due to its unclear mechanism, PDT's application and efficacy were limited. Notch signaling pathway, which is highly correlates with carcinogenesis and development of cervical cancer, could be a potential therapeutic targets to improve the effectiveness of PDT. Therefore, in this study, we explored the effects of Notch signaling pathway in cervical cancer by curcumin mediated PDT with/without Notch receptor blocker (DAPT), and hope to elucidate its mechanism.
Firstly, the effect on the proliferation of cervical cancer Me180 cells were detected with MTT assay, and apoptosis were detected with Annexin V-FITC/PI combined with flow cytometry. Secondly, after establishment of nude mice model, dividing the experimental animals into model group, curcumin PDT group, simple DAPT group, and curcumin-PDT+DAPT group, and analyzing tumor volume changes as well as HE staining in each group. mRNA and protein expression of gene Notch-1 and its downstream NF-κB and VEGF were observed with RT-PCR, immunohistochemical staining and Western-blot with/without inhibition of Notch signaling pathway by DAPT, both in vivo and in vitro experiments.
We found both DAPT and curcumin-PDT can inhibit the proliferation and induce apoptosis of cervical cancer cell. The two have synergistic effect in vitro and in vivo. This effect can effectively block the conduction of Notch signaling pathway, which is associated with down-regulation of the expression of Notch1 and NF-κB. Notch signaling pathway could be one of the targets of curcumin-PDT photodynamic therapy.
Keywords: Notch signaling, DAPT, Photodynamic therapy, Curcumin, Cervical cancer.