Liu Yufang, Xie Yang, Lin Yao, Xu Qingfang, Huang Yunfen, Peng Mengran, Lai Wei, Zheng Yue
Department of Dermatology and Venereology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Bioeng Biotechnol. 2020 Dec 1;8:601969. doi: 10.3389/fbioe.2020.601969. eCollection 2020.
The incidence of primary cutaneous melanoma continues to increase annually and is one of the most aggressive malignancies in humans and need to develop more novel non-surgical therapies. Autophagy and cathepsin B targeted therapy was reported to improve melanoma treatment. Cepharanthine (CEP), a natural alkaloid extracted from the genus Cephalophyllum has been reported to have the function of inhibiting cancers. We found that CEP inhibited human primary cutaneous melanoma cells viability and proliferation in 24 h , and topical application or intra-tumoral injection of CEP decreased the growth of cutaneous melanoma in mice within 4 weeks. CEP preparations below 50% concentration did not induce skin irritation and allergy reaction on human skin . Primary cutaneous melanoma cells incubated with CEP, the expression of cathepsin B was decreased and the LC3-I and LC3-II expression changed in a dose-dependent manner, while p53, p21Cip1p, and p16Inka gene expression was up-regulated. We demonstrated the effects of CEP as a novel tumor-regional therapy for cutaneous melanoma and provided a preliminary research basis for future clinical treatment researches and the exploration of integrated treatments with systemic therapy, radiotherapy, and surgery for human primary cutaneous melanoma.
原发性皮肤黑色素瘤的发病率每年持续上升，是人类最具侵袭性的恶性肿瘤之一，需要开发更多新型非手术治疗方法。据报道，自噬和组织蛋白酶B靶向治疗可改善黑色素瘤治疗。千金藤素（CEP）是从千金藤属植物中提取的一种天然生物碱，据报道具有抑制癌症的作用。我们发现，CEP在24小时内可抑制人原发性皮肤黑色素瘤细胞的活力和增殖，局部应用或瘤内注射CEP可在4周内抑制小鼠皮肤黑色素瘤的生长。浓度低于50%的CEP制剂不会对人体皮肤引起皮肤刺激和过敏反应。用CEP处理原发性皮肤黑色素瘤细胞后，组织蛋白酶B的表达降低，LC3-I和LC3-II的表达呈剂量依赖性变化，而p53、p21Cip1p和p16Inka基因的表达上调。我们证明了CEP作为一种新型皮肤黑色素瘤肿瘤区域治疗方法的效果，并为未来人类原发性皮肤黑色素瘤的临床治疗研究以及与全身治疗、放疗和手术的综合治疗探索提供了初步研究基础。
