title: [Anti-MDR tumor mechanism of CIP-36, a podophyllotoxin derivative].
abstract: This study is to investigate the antitumor activity of CIP-36 on multidrug resistant human oral squamous carcinoma cell line (KBV200 cells) in vitro and the possible anticancer mechanisms. MTT assay, Hoechst fluorescein stain, RT-PCR and immunohistochemistry were carried out on KBV200 and KB cells. The growth of many tumor cells was obviously inhibited by CIP-36, especially the multidrug resistant cells KBV200. Obvious apoptosis could be observed in the Hoechst 33342 staining experiments. The results of RT-PCR showed that the levels of p53, p21, caspase-3 and bax mRNA increased, and meanwhile the expression of mdr-1 and bcl-2 mRNA decreased in a dose-dependent manner. The data were significantly different from that of vehicle. The expression of P-gp significantly decreased with the increasing dosage of CIP-36 examined by immunohistochemistry. It can be concluded that CIP-36 could change resistance-related genes and proteins to overcome multidrug resistance in the KBV200 cell line.
authors.affiliation: Department of Pharmacognosy, Medical College of Chinese People's Armed Police Forces, Tianjin 300162, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mei
authors.forename: Yun-gen
authors.initials: YG
authors.lastname: Jiang
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Lü
authors.forename: Ke-zhu
authors.initials: KZ
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007624:KB Cells; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D011034:Podophyllotoxin