title: HOXC6 regulates the antitumor effects of pheophorbide a-based photodynamic therapy in multidrug-resistant oral cancer cells.
abstract: Photodynamic therapy (PDT) has been considered to be a possible candidate approach for the treatment of multidrug-resistant (MDR) cancer. To investigate the photocytotoxicity of pheophorbide a-based PDT on MDR cells, the intracellular pathways were studied using the human oral cancer FaDu cell line and its paclitaxel-selected subline FaDu-PTX. Pheophorbide a (Pa)-PDT induced significant photocytotoxicity in both FaDu and FaDu-PTX cell lines with cell apoptosis greater in FaDu cells compared to FaDu-PTX cells. We found that Hoxc6 and MDR-1 expression was strongly detected in FaDu-PTX cells compared to FaDu cells. Intriguingly, Pa-PDT effectively reduced Hoxc6 and MDR-1 expression in FaDu-PTX cells. The siRNA for HOXC6 can inhibit the intracellular MDR-1 levels in FaDu-PTX cells and induce the phototoxic effects of Pa-PDT. Furthermore, our in vivo studies showed that the Pa-PDT and HOXC6 siRNA significantly reduce the growth of FaDu-PTX xenograft tumors in C3H mice compared with control- and PTX-treated tumors. Histopathology was also used to confirm this antitumor effect. Pa-PDT may be a potential therapeutic modality for multidrug-resistant cancer, and Hoxc6, as a possible contributor to MDR, may reduce the therapeutic potential in multidrug-resistant oral malignancies.
authors.affiliation: Department of Biochemistry, Oriental Medicine, Dongguk University, Gyeongju 780-714, Republic of Korea.
authors.forename: Soo-A
authors.initials: SA
authors.lastname: Kim
authors.affiliation: Department of Pathology, College of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Mi Rha
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Pathology, College of Dentistry, Wonkwang University, Daejeon 302-120, Republic of Korea.
authors.forename: Jung-Hoon
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Pathology, College of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
authors.forename: Sang-Gun
authors.initials: SG
authors.lastname: Ahn
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003131:Combined Modality Therapy / Q000379:methods*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D017239:Paclitaxel / Q000627:therapeutic use; D010610:Pharyngeal Neoplasms / Q000628:therapy*; D010614:Pharynx / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000972:Antineoplastic Agents, Phytogenic; C094289:HOXC6 protein, human; D018398:Homeodomain Proteins; D017319:Photosensitizing Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D002734:Chlorophyll; C032623:pheophorbide a; D017239:Paclitaxel