Takemura Y, Ohnuma T, Sekiguchi S
Department of Laboratory Medicine, National Defense Medical College, Saitama, Japan.
Keio J Med. 1991 Jun;40(2):78-81. doi: 10.2302/kjm.40.78.
The influence of tumor cell density on the antitumor effect of doxorubicin (DXR) in combination with cisplatin (CDDP) was studied in vitro using DND-39A lymphoma cells. DXR was progressively less effective on colony formation inhibition when cell density was increased from 10(5) to 10(8) viable cells/ml (positive inoculum effect), whereas the effect of CDDP was not influenced by cell densities. At a density of 10(5) cells/ml, inhibition of colony formation was virtually identical irrespective of cells being exposed to DXR and CDDP either simultaneously or sequentially. When cell density was increased to 10(7) and 10(8) cells/ml, sequential exposure to CDDP followed by DXR was more active than simultaneous or reversed order of exposure to the two drugs. These results indicate that for DXR-CDDP combination chemotherapy against the cells at high density, the proper sequence of the treatment should be the administration of CDDP followed by DXR, rather than simultaneous or reversed order of exposure. Inoculum effect may be an additional determinant for the rational development of combination chemotherapy.
利用DND - 39A淋巴瘤细胞在体外研究了肿瘤细胞密度对阿霉素（DXR）联合顺铂（CDDP）抗肿瘤作用的影响。当细胞密度从10⁵个活细胞/毫升增加到10⁸个活细胞/毫升时，DXR对集落形成抑制的效果逐渐降低（阳性接种效应），而CDDP的效果不受细胞密度的影响。在细胞密度为10⁵个细胞/毫升时，无论细胞是同时还是先后暴露于DXR和CDDP，集落形成的抑制情况几乎相同。当细胞密度增加到10⁷和10⁸个细胞/毫升时，先给予CDDP后给予DXR比同时给药或颠倒两种药物的给药顺序更有效。这些结果表明，对于高密度细胞的DXR - CDDP联合化疗，合适的治疗顺序应该是先给予CDDP，然后给予DXR，而不是同时给药或颠倒给药顺序。接种效应可能是联合化疗合理开发的另一个决定因素。
