title: Transcriptomic analysis of the effect of ifosfamide on MDCK cells cultivated in microfluidic biochips.
abstract: We investigated the behavior of renal cells cultivated in microfluidic biochips when exposed to 50 μM of ifosfamide, an antineoplastic drug treatment. The microarray analysis revealed that ifosfamide had any effect in Petri conditions. The microfluidic biochips induced an early inflammatory response in the MDCK in the untreated cells. This was attributed to cells adapting to the dynamics and micro environment created by the biochips. This led to modulations in the mitochondria dysfunction pathway, the Nrf-2 and oxidative stress pathways and some related cancer genes. When exposed to 50 μM of ifosfamide, we detected a modulation of the pathways related to the cancer and inflammation in the MDCK cultivated in the biochips via modulation of the ATM, p53, MAP Kinase, Nrf-2 and NFKB signaling. In addition, the genes identified and related proteins affected by the ifosfamide treatment in the biochips such as TXNRD1, HSP40 (DNAJB4 and DNAJB9), HSP70 (HSPA9), p21 (CDKN1A), TP53, IKBalpha (NFKBIA) are reported to be the molecular targets in cancer therapy. We also found that the integrin pathway was perturbed with the ifosfamide treatment. Finally, the MYC proto-oncogene appeared to be a potential bridge between the integrin signaling and the anti-inflammatory response.
authors.affiliation: CNRS UMR 7338, Laboratoire de Biomécanique et Bio ingénierie, Université de Technologie de Compiègne, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Choucha Snouber
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacques
authors.forename: Matthieu
authors.initials: M
authors.lastname: Monge
authors.forename: Cécile
authors.initials: C
authors.lastname: Legallais
authors.forename: Eric
authors.initials: E
authors.lastname: Leclerc
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D020869:Gene Expression Profiling / Q000295:instrumentation / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects*; D007069:Ifosfamide / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics; D007668:Kidney / Q000166:cytology; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide