|
|
|
| Effects of Curcumin-mediated Photodynamic Therapy on Notch Signaling Pathway in a Rat Model of Cervical Cancer |
| LIU Hong-lian, LIU Zhao-sheng |
| Longyan First Affiliated Hospital of Fujian Medical University, Longyan Fujian Province 364000, China |
|
|
|
|
Abstract Objective: To investigate the effect of curcumin-mediated photodynamic therapy(PDT) on the Notch signaling pathway in a rat model of cervical cancer. Methods: A total of 70 SPF-grade healthy adult female Wistar rats were selected, and were randomly divided into 5 groups using a random number table: model group, positive group, curcumin group, PDT group, and PDT+curcumin group. The rat model of cervical cancer was constructed by intraperitoneal injection of U14 cells (5×106/mL) 1mL. After successful modeling, the model group was given intraperitoneal injection of normal saline+natural light, and the positive group was intraperitoneally injected with 100 mg/kg DAPT solution+Natural light, the curcumin group was given intraperitoneal injection of 200 μL of 150 μmol/L curcumin+natural light, the PDT group was given intraperitoneal injection of normal saline+photodynamic therapy at 100 J/cm2, and the PDT+curcumin group was given intraperitoneal injection of 200 μL of 150 μmol/L curcumin+photodynamic therapy at 100 J/cm2. Results: HE staining results showed that PDT+ curcumin group exhibited a more sparse arrangement of tumor cells in the lesion tissue slices, relatively smaller cell volume, lower nuclear-cytoplasmic ratio, and more condensed nuclei, with a noticeable presence of vesicular nuclei and perinuclear halos than the other four groups. The expression of Notch-1 protein in PDT+curcumin group, as measured by immunohistochemistry and Western blotting, was significantly lower than that in other four groups (P<0.05). CD4+, CD8+ and CD4+/CD8+ expression levels in PDT+curcumin group were higher than those in model group, positive group and PDT group (P<0.05). The expression of Bcl-2 protein in PDT+curcumin group was lower than that in the other four groups, and the expression of Bax protein in PDT+curcumin group was higher than that in the other four groups (P<0.05). Conclusion: Curcumin-mediated PDT can inhibit Notch signaling pathway, promote immune factors, and regulate the expression of apoptosis-related proteins such as Bcl-2 and Bax.
|
|
Received: 22 March 2024
|
|
|
|
Corresponding Authors:
LIU Hong-lian. E-mail: liu hong lian2013@163.com
|
|
|
|
[1] Singh D, Vignat J, Lorenzoni V, et al.Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative[J]. Lancet Glob Health, 2023, 11(2): e197-e206.
[2] Park W, Cho S, Han J, et al.Advanced smart-photosensitizers for more effective cancer treatment[J]. Biomater Sci, 2017, 6(1): 79-90.
[3] Shanazarov N, Bariyeva G, Avdeyev A, et al.Evaluation of the effectiveness and safety of photodynamic therapy in the treatment of precancerous diseases of the cervix (neoplasia) associated with the human papillomavirus: A systematic review[J]. Photodiagnosis Photodyn Ther, 2024, 45: 103925.
[4] Zhou Lijun, Zhang Yan, Ren Lirong.Research on the proliferation, apoptosis and expression of Hela cells of cervical cancer cell lines by photodynamic therapy[J]. Maternal and Child Health Care of China, 2018, 33(24): 5974-5976.
(周莉君, 张燕, 任利容. 光动力疗法对宫颈癌细胞株Hela细胞增殖凋亡及表达情况研究[J]. 中国妇幼保健, 2018, 33(24): 5974-5976.)
[5] Chen Hongmei, Feng Qiang, Li Juan, et al.The effects and mechanisms of curcumin on tumor cell apoptosis and immune function in rats with cervical cancer[J]. Chinese Journal of Gerontology, 2023, 43(13): 3271-3274.
(陈红梅, 冯强, 黎娟, 等. 姜黄素对宫颈癌大鼠肿瘤细胞凋亡、免疫功能的影响及作用机制[J]. 中国老年学杂志, 2023, 43(13): 3271-3274.)
[6] Mu Tianlong, Liu Huimin, Pan Yanshu, et al.Multi-dosephotodynamic combines with curcumin in the treatment of xenograft tumor of cervical cancer and the expression of TNF-α and Caspase-8[J]. Global Traditional Chinese Medicine, 2022, 15(4): 543-549.
(牟天龙, 刘慧敏, 潘彦舒, 等. 多剂量光动力联合姜黄素治疗宫颈癌体外移植瘤及肿瘤组织中肿瘤坏死因子-α、半胱氨酸蛋白酶-8的表达研究[J]. 环球中医药, 2022, 15(4): 543-549.)
[7] Shi Yali, Jiang Jing.Research progress of Notch signaling pathway in cervical cancer[J]. Chinese Journal of Clinical Obstetrics and Gynecology, 2016, 17(3): 286-288.
(石亚利, 江静. Notch信号通路在宫颈癌中的研究进展[J]. 中国妇产科临床杂志, 2016, 17(3): 286-288.)
[8] Ashall V, Morton D, Clutton E.A Declaration of Helsinki for animals[J]. Vet Anaesth Analg, 2023, 50(4): 309-314.
[9] Tan Yandi, Zhao Yun, Liu Chaoqi, et al.Application progresses of photodynamic and sonodynamic therapy for malignant gynecologic neoplasms[J]. Chinese Journal of Medical Imaging Technology, 2020, 36(9): 1388-1391.
(谭妍迪, 赵云, 刘朝奇, 等. 光声动力疗法在妇科恶性肿瘤中的应用进展[J]. 中国医学影像技术, 2020, 36(9): 1388-1391.)
[10] He Guifang, Mu Tianlong, Pan Yanshu, et al.Inhibitory effect of DAPT on Notch signaling pathway in curcumin mediated photodynamic therapy for cervical cancer xenografts in nude mice[J]. National Medical Journal of China, 2018, 98(19): 1511-1516.
(贺桂芳, 牟天龙, 潘彦舒, 等. DAPT抑制Notch信号通路在姜黄素介导光动力治疗宫颈癌裸鼠移植瘤的机制研究[J]. 中华医学杂志, 2018, 98(19): 1511-1516.)
[11] Zagouras P, Stifani S, Blaumueller CM, et al.Alterations in Notch signaling in neoplastic lesions of the human cervix[J]. Proc Natl Acad Sci U S A, 1995, 92(14): 6414-6418.
[12] Daniel B, Rangarajan A, Mukherjee G, et al.The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions[J]. J Gen Virol, 1997, 78(Pt5): 1095-1101.
[13] Wang Jing, Shen Changjiu, Shen Xiaowen, et al.The expression of peripheral blood regulatory T-cells and T-cell subsets in elderly patients with cervical cancer and their relationship with the clinicopathological features of cervical cancer[J]. Chinese Journal of Gerontology, 2019, 39(21): 5222-5224.
(王静, 沈长久, 沈晓雯, 等. 老年宫颈癌患者外周血调节性T细胞及T细胞亚群表达及其与宫颈癌临床病理特点的关系[J]. 中国老年学杂志, 2019, 39(21): 5222-5224.)
[14] Delbridge AR, Grabow S, Strasser A, et al.Thirty years of BCL-2: translating cell death discoveries into novel cancer therapies[J]. Nat Rev Cancer, 2016, 16(2): 99-109.
[15] Robin AY, Iyer S, Birkinshaw RW, et al.Ensemble properties of Bax determine its function[J]. Structure, 2018, 26(10): 1346-1359.
[16] Cao Yi, Wang Li, Yang Xiaohong, et al.Effects of curcumin on proliferation inhibition and the expression of Notch-1,Bax and Bak in HaCaT cells[J]. The Chinese Journal of Dermatovenereology, 2011, 25(7): 506-508.
(曹毅, 王莉, 杨晓红, 等. 姜黄素对HaCaT增殖的抑制作用及对Notch-1,Bax和Bak表达的影响[J]. 中国皮肤性病学杂志, 2011, 25(7): 506-508.) |
|
|
|
