In the liver implanted group, 2 mice developed abdominal dropsy, but no cachexia or death occurred. After 8 wks, all nude mice
were sacrificed. The general morphology of the implanted tumor in both the experimental and control groups showed no significant difference. Tumors assumed an ellipse or irregular sublobe morphology. Under electron microscope, the tumor MGCD0103 mouse cells share many similarities with human hepatocellular carcinoma cells, including enlarged nuclei, hyperchromatic nucleoli, and multiple nuclear P005091 membrane incisures (Figure 1). The mean tumor weight was 1.48 ± 0.21 g. Fibrous tissue abundantly surrounded the tumor. The incisal surface of the tumor body was gray. The minority of tumors showed a scattered and clustered distribution. In addition, three
mice exhibited metastases in the abdominal cavity in the liver implanted group. Figure 1 Under electron microscope, the tumor cells share many similarities with human hepatocellular carcinoma cells, including enlarged nuclei, hyperchromatic nucleoli, and multiple nuclear membrane incisures. (×10000). Observation of cell morphology Under a phase contrast microscope, Bel-7402 cells were fusiform, aligned and compact with well-distributed sizes, distinct boundaries and growth with adherence. Batimastat concentration After the addition of drugs, the majority of cells appeared apoptotic and subsequently dissolved. The size of the surviving cells was unequal, the cellular profile was unclear and adherence was reduced. After about two weeks, cell growth recovered and the above variations in the acute stage had disappeared. The morphology of resistant-cells
was irregular, with slightly augmented volume, which signifies accumulated growth. Massive particles and vacuoles appeared in the cytoplasm and the nucleus exhibited slight shrinkage. Sensitivity of the three types of cell sub-lines toward anticancer drugs (Table 1) Table 1 indicates that the three resistant cell sub-lines generated cross-resistance Astemizole toward ADM and CDDP but showed no cross-resistance to mitomycin (MMC), methotrexate (MTX), 5 -fluorouracid (5- FU). Table 1 Sensitivity of Bel-7402/ADMS, Bel-7402/ADML and Bel-7402/ADMV cells to multiple chemotherapy drugs. Drug IC50(mg.L-1, ± s) RI Bel-7402 Bel-7402/ADM S Bel-7402/ADM L Bel-7402/ADM V RI S RI L RI V ADM 2.09 ± 0.13 26.69 ± 0.46 26.92 ± 0.38 46.93 ± 0.82 12.77 12.88 22.45 CDDP 0.98 ± 0.11 12.92 ± 3.45 13.46 ± 3.00 25.18 ± 3.57 13.18 13.73 25.69 MMC 0.54 ± 0.05 0.57 ± 0.08 0.60 ± 0.08 0.62 ± 0.04 1.06 1.11 1.15 MTX 0.15 ± 0.05 0.17 ± 0.05 0.20 ± 0.06 0.21 ± 0.05 1.13 1.33 1.4 5-FU 119.65 ± 6.46 120.78 ± 4.84 121.60 ± 6.15 123.66 ± 5.00 1.01 1.02 1.03 Note: By least significant difference (LSD) paired-comparison in both ADM and CDDP groups, except Bel-7402/ADML vs. Bel-7402/ADMS (P > 0.05), there is no statistical significance. In other groups of resistant cells, there is a significant difference by paired-comparison.