A new in vivo assay of the reactions of microencapsulated human tumor cells to chemotherapeutic drugs.
A new cell culture modality had already been established in our laboratory. Using this model, living KB and GBM 8401 tumor cells grew and proliferated exponentially in semipermeable microcapsules, implanted in vivo. The culture method was designed as a modality for a predictive anticancer drug sensitivity test. Its advantages included providing a three-dimensional growth and in vivo supply of nutrients. Tumor cell sensitivity to drugs can be assessed in vivo. The assay is applicable to virtually all histological types of human tumor cells. Using this technique, anticancer drug sensitivity tests of KB and GBM 8401 cells were evaluated. The results showed that such encapsulated cells grew and proliferated rapidly. In addition, the proliferation of KB cells was more rapid than that of GBM 8401 cells under conventional monolayer and in vivo microcapsule culture states. They were very sensitive to adriamycin and fluorouracil, and relatively resistant to cyclophosphamide while cultured in vitro. The viability percentage of microencapsulated KB cells cultured in vivo for two weeks was around 80-90%, roughly similar to that of the same cells conventionally cultured in vitro. However, the proliferation rates of encapsulated KB and GBM 8401 cells in vivo were significantly inhibited by all the drugs tested, with KB cells inhibited more significantly than GBM 8401. These results also suggest that some anticancer drugs needing to be bioactivated in vivo had better test results by this technique, and thus false negative results could be excluded. Also, the good repair capacity of microcapsules implanted in vivo, for damaged tumor cells previously incubated with chemotherapeutic drugs, appears to provide a much better environment for cell growth because much essential nourishment can be supplied. The inhibition percentage of fluorouracil to encapsulated cancer cells from patients with adenocarcinoma of the colon was also tested; they were 69.8% in vivo and 76.5% in vitro. This fast, relatively inexpensive in vivo model can be used to screen various anticancer drugs and help clinical oncologists to select the most effective agents for individual patients.
Department of Radiation Oncology, Tri-Service General Hospital, Taipei, Taiwan, R.O.C.
J M
JM
Hwang
C F
CF
Chen
W L
WL
Hsu
K Y
KY
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents