ackgroud : Recently, attention has been focused on the possibility of predicting the
effectiveness of anticancer drugs against individual tumors through chemosensitivity test. The
MTT assay is a preferable, accurate, and convenient colorimetric assay which is based on the
premise that the mitochondria of living cells reduce the tetrazolium salt to formazan. It has
been suggested that malignant neoplasms contaion multiple cell populations exhibiting
tremendous biologic heterogeneity. Particularly the detailed differences in chemosensitivity
between cells from primary and from metastasis lesions remain unsolved. This study was
designed to assess the usefulness of in vitro chemosensitivity tests in the treatment of gastric
cancers and differences in chemosensitivity between gastric cancer cells cultured from primary
and metastatic lesions.
Method : Primary cancer cells of 138 patients with gastric cancer (group A), obtained
through the endoscopic biopsy or surgical open biopsy, and metastatc cancer cells of 26
patients (group B:27 lesions), obtained through the paracentesis or pleural centesis, were
cultured using culture medium supplemented with 20% fetal bovine serum. The colorimetric
MTT assay was applied for in vitro chemosensitivity tests.
Results :
1) The success tates of short-term culture of gastric cancer cells were 14.5% (20/138) in
group A and 66.7% (18/27)in group B, respectively.
2) The morphology of the cultured cells observed through phase-contrast and light
microscopy showed no significant difference between group A and B.
3) The mean IC50 of ADR and MMC were significantly higher in group B than group
A(p<0.05) and that of VP-16 significantly higher in group A(p<0.001)
4) The two-drug combination regimens having the statistically significant synergistic
effects were ADR + MMC (p<0.05) and ADR+DDP(p=0.01) in group A, ADR+VP-16 (p<0.05),
5-FU+VP-16(p<0.05), and MMC+VC-16(p<0.05) in group B, and the three-drug combination
regimens were 5-FU+ADR+DDP (P<0.01) in group B.
5) The two-drug combination regimens having the supraaddictive effects over 70% of the
cases were ADR+MMC and ADR+DDP in group A, ADR+VP-16, 5-FU+VP-16, and
DDP+VP-16 in group B, and the threedrug combination regimens 5-FU+ADR+DDP and
MMC+DDP+5-FU in group A, 5-FU+ADR+VP-16 and VP-16+ADR+DDP in group B.
6) The combination regimens having synergistic effects were different between group A
and group B. 5-FU+ADR+MMC and 5-FU+ADR+DDP combination had synergistic effects in
group A, but antagonistic effects in group B. 5-FU+ADR+VP-16 and VP-16+ADR+DDP
combination synergistic effects in group B, but antagonistic effects in group A.
Conclusion : The chemosensitivities of gastric cancer cells were significantly different
between the primary and metastatic lesions from which the cultured cells were derived.
Thus, the individual chemosensitivity test using short-term culture system may be useful for
the selection of the most effective anticancer drugs.
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