title: Silencing of CD59 enhanced the sensitivity of HT29 cells to 5-Fluorouracil and Oxaliplatin.
abstract: Complement regulatory proteins (CD55 and CD59) were known to be expressed in many tumors and tumor cell lines including colorectal carcinoma, and were proposed as immunotherapy targets, however whether knocking down of CD55 and CD59 will affect the sensitivity of HT-29 cells to chemotherapy drugs for example, 5-Fluorouracil and Oxaliplatin and their possible mechanisms haven't been studied. To address this question, SiRNAs targeting CD55 and CD59 were chemically synthesized and transfected into HT-29 cells by lipofectamine. HT-29 growth curves of CD55 and CD59 knockdown cells were detected by MTT assay, HT29 inhibition curves to chemotherapy drugs (5-Fu and Oxaliplatin) were also assayed, in addition, chemotherapy sensitivity changes of HT29 affected by CD55 and CD59 knockdown were equally detected. Complement mediated lysis was examined by calcein-AM. We found that silencing CD59 in HT-29 cells could significantly enhance their sensitivity to 5-FU (P < 0.05) and Oxaliplatin (P < 0.05), and significantly reduced their IC50 concentration. On the contrary, knocking down of CD55 could inhibit HT-29 growth (P < 0.05). Mechanisms included increasing apoptosis rate of HT-29 by CD59 knocking down and G1/G0 blocking by silencing CD55. Our results thus shed light on the novel mechanism of chemotherapy resistance and provide an alternative strategy to overcome the resistance problem.
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Key Laboratory for Rare and Uncommon Diseases, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, PR China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Yin
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Key Laboratory for Rare and Uncommon Diseases, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, PR China. Electronic address: cuilingli@yahoo.com.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Li
authors.affiliation: Image Center, The Third People's Hospital in Jinan City, Jinan, 250101, PR China.
authors.forename: Shaoyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Key Laboratory for Rare and Uncommon Diseases, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Key Laboratory for Rare and Uncommon Diseases, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Ren
authors.affiliation: Key Laboratory for Tumor Immunology and Traditional Chinese Medicine Immunology, Key Laboratory for Rare and Uncommon Diseases, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, PR China. Electronic address: jiangguosh@163.com.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Jiang
mesh_terms: D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D018958:CD55 Antigens / Q000235:genetics / Q000378:metabolism; D018957:CD59 Antigens / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D005472:Fluorouracil / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D000077150:Oxaliplatin; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018958:CD55 Antigens; D018957:CD59 Antigens; D009944:Organoplatinum Compounds; D034741:RNA, Small Interfering; D000077150:Oxaliplatin; C051590:CD59 protein, human; D005472:Fluorouracil
keywords: 5-Fluorouracil; CD55; CD59; Chemotherapy sensitivity; HT-29; Oxaliplatin