Electrochemical monitoring of rat mammary adenocarcinoma cells: an in vitro assay for anticancer drug selection.
We report the application of an electrochemical biosensor (Oncoprobe; Marks & Clerk, Manchester, UK) to determine whether changes in the open circuit potential (OCP) of rat mammary adenocarcinoma cells (MTLn3) treated in vitro with four cytotoxic anticancer drugs could predict their effects in vivo. MTLn3 cells were seeded onto sensors, then exposed to each anticancer compound (cisplatin, doxorubicin, paclitaxel, or vinblastine), and monitored for 44 hours. Electrochemical monitoring in vitro detected OCP responses to all four drugs, with cisplatin and doxorubicin producing greater changes over a shorter period than vinblastine and paclitaxel. Syngeneic MTLn3 cells were used to generate palpable tumors in 50 female Fischer 344 rats. Animals were divided into five equal groups; on day 12 four of the groups received an anticancer drug, and one received a saline control. Fourteen days later the animals were killed, and primary tumor weights were determined. Tumors from cisplatin- and doxorubicin-treated rats were significantly reduced in weight compared to the control, paclitaxel-, and vinblastine-treated groups. The anticancer drug-induced changes observed through real-time electrochemical monitoring of MTLn3 cells in vitro correlated well with the in vivo animal model, unlike the conventional end-point assays of lactate dehydrogenase release and Alamar Blue.
Adlam
Daman J
DJ
University Department of Medicine, University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom.
Dabbous
Mustafa K
MK
Woolley
David E
DE
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods / Q000639:trends; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D016903:Drug Monitoring / Q000295:instrumentation / Q000379:methods / Q000639:trends; D055664:Electrochemical Techniques / Q000295:instrumentation* / Q000379:methods*; D005260:Female; D005544:Forecasting / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000737:chemistry; D015674:Mammary Neoplasms, Animal / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology*; D008564:Membrane Potentials / Q000187:drug effects; D010078:Oxazines / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344 / Q000378:metabolism; D014966:Xanthenes / Q000737:chemistry
D000970:Antineoplastic Agents; D010078:Oxazines; D014966:Xanthenes; C005843:resazurin; D004247:DNA; D007770:L-Lactate Dehydrogenase