title: Conditionally replicative adenovirus-based mda-7/IL-24 expression enhances sensitivity of colon cancer cells to 5-fluorouracil and doxorubicin.
abstract: BACKGROUND
  Multiple drug resistance (MDR) greatly limits the efficacy of chemotherapy for colon cancer. An adenovirus armed with Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24; abbreviated to 'IL-24' here) was shown to reverse the MDR of colon cancer cells to oxaliplatin and doxorubicin. However, the relatively low expression level of IL-24 mediated by a replication-deficient adenoviral vector hindered its clinical application.
  
  
  METHODS
  To enhance IL-24-dependentreversion of the MDR phenotype, we utilized a conditionally replicative adenoviral vector, AdBB-IL24, to express IL-24 at a high level for more efficient MDR reversion.
  
  
  RESULTS
  An enzyme-linked immunosorbent assay (ELISA) suggested conditionally replicative adenoviral vector-mediated IL-24 expression was elevated in comparison with that of a replication-deficient adenoviral vector, Ad-IL24. AdBB-IL24 was shown to reverse MDR in colon cancer cells more potently than Ad-IL24. The AdBB-IL24-induced MDR reversion was linked to reduced P-glycoprotein (Pgp) and breast cancer resistance protein 1 (BCRP1) expression. Consistently, 5-fluorouracil and doxorubicin induced more apoptosis in AdBB-IL24-infected colon cancer cells compared with that in the Ad-IL24-infected cells. A cell viability assay showed that AdBB-IL24 could enhance the growth-inhibitory effect of 5-fluorouracil and doxorubicin on colon cancer cells more effectively than Ad-IL24 in vitro. In a mouse model, we also found that the combination of 5-fluorouracil and doxorubicin with AdBB-IL24 completely inhibited the growth of colon cancer cells.
  
  
  CONCLUSIONS
  We here provide evidence supporting conditionally replicative adenoviral vector-based gene therapy as a powerful strategy to enhance mda7/IL-24-dependent MDR reversion of colon cancer cells.
authors: Department of Hepatobiliary Surgery, The First People's Hospital of Yunnan Province, Kunhua Hospital Affiliated to Kunming Medical College, Kunming, China.
authors: Jing
authors: J
authors: Xu
authors: Yiwo
authors: Y
authors: Mo
authors: Xiaoyun
authors: X
authors: Wang
authors: Jun
authors: J
authors: Liu
authors: Xinjin
authors: X
authors: Zhang
authors: Junfeng
authors: J
authors: Wang
authors: Lei
authors: L
authors: Hu
authors: Chao
authors: C
authors: Yang
authors: Lei
authors: L
authors: Chen
authors: Yankun
authors: Y
authors: Wang
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000502:physiology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin; D005472:Fluorouracil; D007378:Interleukins; D009363:Neoplasm Proteins; D000099180:Interleukin-24