JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2015, Vol. 53 ›› Issue (1): 21-26.doi: 10.6040/j.issn.1671-7554.0.2014.581

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Effects of TMPyP4-PDT on human immortal cervical epithelial H8 cells

ZONG Liju1, ZHANG Youzhong1, WANG Jie1, WU Shuxia1, LIU Hongli1, ZHANG Lu2   

  1. 1. Department of Gynecology and Obstetrics, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    2. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, Gansu, China
  • Received:2014-09-05 Revised:2014-10-29 Published:2015-01-10

Abstract: Objective To investigate the effects of photosensitizer 5, 10, 15, 20-Tetrakis (1-methylpyridinium-4-yl) porphyrin based-photodynamic therapy (TMPyP4-PDT) on the proliferation and apoptosis of human immortal cervical epithelial H8 cells. Methods The morphological changes were observed by inverted microscope. Proliferative viability was evaluated with Cell Counting Kit-8. Apoptosis was assessed by Annexin V-FITC/PI Apoptosis Detection Kit. The p16INK4a expression was evaluated by immunocytochemistry Strept Avidin-Biotin-enzyme Complex (SABC) method. Human telomerase reverse transcriptase (hTERT) and p21 expression were analyzed by Western blotting. Results TMPyP4-PDT could inhibit H8 cellular proliferative viability and induce apoptosis in a TMPyP4 dose-dependent manner. Immunocytochemistry analysis revealed that TMPyP4-PDT could reduce the positive rate of p16INK4a protein in H8 cells. Western blotting results indicated that TMPyP4-PDT could downregulate hTERT protein expression while upregulate p21 protein in H8 cells. Conclusion TMPyP4-PDT can inhibit H8 cell proliferation and induce apoptosis. The possible mechanism is related to down-regulation of p16INK4a and hTERT, as well as up-regulation of p21 protein.

Key words: 5, 10, 15, 20-Tetrakis (1-methylpyridinium-4-yl) porphyrin- photodynamic therapy, p21 protein, Cervix neoplasms, H8 cells, Human telomerase reverse transcriptase, p16INK4a protein

CLC Number: 

  • R454.2
[1] Arbyn M, Castellsague X, de Sanjose S, et al. Worldwide burden of cervical cancer in 2008[J]. Ann Oncol, 2011, 22(12): 2675-2686.
[2] Kalliala I, Dyba T, Nieminen P, et al. Mortality in a long-term follow-up after treatment of CIN[J]. Int J Cancer, 2010, 126(1): 224-231.
[3] Khan MJ, Smith-McCune KK. Treatment of cervical precancers: back to basics[J]. Obstet Gynecol, 2014, 123(6): 1339-1343.
[4] Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an update[J]. CA Cancer J Clin, 2011, 61(4): 250-281.
[5] Tada-Oikawa S, Oikawa S, Hirayama J, et al. DNA damage and apoptosis induced by photosensitization of 5,10,15,20-tetrakis (N-methyl-4-pyridyl)-21H,23H-porphyrin via singlet oxygen generation[J]. Photochem Photobiol, 2009, 85(6): 1391-1399.
[6] Lu Y, Zheng L, Zhang W, et al. Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro[J]. Gynecol Oncol, 2014, 134(2): 364-371.
[7] Choi MC, Jung SG, Park H, et al. Fertility preservation via photodynamic therapy in young patients with early-stage uterine endometrial cancer: a long-term follow-up study[J]. Int J Gynecol Cancer, 2013, 23(4): 698-704.
[8] Zamiri B, Reddy K, Macgregor RB, Jr., et al. TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins[J]. J Biol Chem, 2014, 289(8): 4653-4659.
[9] Filip AG, Clichici S, Daicoviciu D, et al. Possible in vivo mechanisms involved in photodynamic therapy using tetrapyrrolic macrocycles[J]. Braz J Med Biol Res, 2011, 44(1): 53-61.
[10] Liu H, Lv C, Ding B, et al. Antitumor activity of G-quadruplex-interactive agent TMPyP4 with photodynamic therapy in ovarian carcinoma cells[J]. Oncol Lett, 2014, 8(1): 409-413.
[11] 丁佰娟, 张友忠, 吕昌帅, 等. TMPyP4-PDT对人宫颈癌细胞的杀伤效应[J]. 山东大学学报:医学版, 2012, 50(11): 53-57. DING Baijuan, ZHANG Youzhong, LV Changshuai, et al. Effects of TMPyP4-PDT on human cervical cancer cells[J]. Journal of Shandong University: Health Sciences, 2012, 50(11): 53-57.
[12] 叶洪楠, 游珂, 郭艳利, 等. P16INK4a及Ki-67免疫细胞化学检测对ASC-US中高级别病变检出的意义[J]. 肿瘤预防与治疗, 2014, 27(1): 6-11. YE Hongnan, YOU Ke, GUO Yanli, et al. The role of P16INK4a and Ki-67 immunocytochemical examination to detect high level of lesion in ASC-US[J]. Journal of Cancer Control and Treatment, 2014, 27(1): 6-11.
[13] 周莉, 孔敏, 李海霞,等. p16在宫颈癌组织中的表达及临床意义[J]. 中国实验诊断学, 2013, 17(9): 1614-1616. ZHOU Li, KONG Min, LI Haixia, et al. Expression and clinical significance of p16 in patients of cervical carcinoma [J]. Chinese Journal of Laboratory Diagnosis, 2013, 17(9): 1614-1616.
[14] Low KC, Tergaonkar V. Telomerase: central regulator of all of the hallmarks of cancer[J]. Trends Biochem Sci, 2013, 38(9): 426-434.
[15] Rapozzi V, Zorzet S, Zacchigna M, et al. Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies[J]. Mol Cancer, 2014, 13:75.doi:/10.1186/1476-4598-13-75.
[16] Mikami-Terao Y, Akiyama M, Yuza Y, et al. Antitumor activity of TMPyP4 interacting G-quadruplex in retinoblastoma cell lines[J]. Exp Eye Res, 2009, 89(2): 200-208.
[17] 李洪林, 尹利荣, 孙俊杰. 宫颈病变中hTERT基因扩增与高危型HPV感染的关系[J]. 天津医药, 2014, 42(2): 127-130. LI Honglin,YIN Lirong,SUN Junjie. Association between hTERT gene amplification and high-risk HPV infection in cervical lesions[J]. Tianjin Medical Journal, 2014, 42(2): 127-130.
[18] Warfel NA, El-Deiry WS. p21WAF1 and tumourigenesis: 20 years after[J]. Curr Opin Oncol, 2013, 25(1): 52-58.
[19] Chan WH. Photodynamic Treatment Induces an Apoptotic Pathway Involving Calcium, Nitric Oxide, p53, p21-Activated Kinase 2, and c-Jun N-Terminal Kinase and Inactivates Survival Signal in Human Umbilical Vein Endothelial Cells[J]. Int J Mol Sci, 2011, 12(2): 1041-1059.
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