Sensitivity to anticancer agents and resistance mechanisms in clear cell carcinoma of the ovary.
Sensitivity to anticancer agents and resistance mechanisms in clear cell carcinoma of the ovary.
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DOI：
10.1111/j.1349-7006.2002.tb01312.x
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发表时间：
2002-06
期刊：
影响因子：
--
通讯作者：
Terakawa N
中科院分区：
文献类型：
--
作者：
Itamochi H;Kigawa J;Sultana H;Iba T;Akeshima R;Kamazawa S;Kanamori Y;Terakawa N
我们进行了本研究以确定卵巢透明细胞癌（CCC）的化疗耐药机制。五种人CCC细胞系（HAC‐2、RMG‐I、RMG‐II、KK和KOC‐7c）用于本研究。采用3 -（4,5 -二甲基噻唑- 2 -基）- 2,5 -二苯基溴化四唑（MTT）法测定细胞对抗癌药物的敏感性，并通过计算每种药物的曲线下分析面积（AUC）来评估药物敏感性。采用逆转录聚合酶链反应（RT‐PCR）检测多药耐药基因（MDR‐1、MRP‐1、MRP‐2）的表达。酶促法测定谷胱甘肽（GSH）浓度。根据超卷曲质粒底物DNA的松弛度测定拓扑异构酶（topo） I的活性。抗癌药物的IC50值差别很大。AUC结果表明，5株细胞系中有3株（RMG‐I、RMG‐II和KK）对紫杉醇（PTX）敏感，3株（HAC‐2、RMG‐I和RMG‐II）对喜树碱（CPT‐11）的活性代谢物7 -乙酯‐10‐羟基喜树碱（SN‐38）敏感，只有1株（HAC‐2）对顺铂（CDDP）敏感。所有细胞系均对丝裂霉素- C （MMC）和依托泊苷（VP - 16）耐药。在所有细胞系中均检测到MRP‐1基因。只有一个细胞系同时表达MRP‐2和MDR‐1基因。除HAC‐2细胞外，MRP基因的表达与CDDP耐药有关，MDR‐1基因的表达与PTX耐药有关。暴露于CDDP或MMC后，所有细胞系的谷胱甘肽浓度均升高。topo - I酶活性与SN - 38反应之间存在显著相关性。本研究揭示了CCC的几种耐药机制，结果表明PTX和CPT‐11可能是治疗CCC的有效药物。
We conducted the present study to determine the chemoresistance mechanisms in clear cell carcinoma of the ovary (CCC). Five human CCC cell lines (HAC‐2, RMG‐I, RMG‐II, KK, and KOC‐7c) were used in this study. The sensitivity of the cells to the anticancer agents was determined by 3–(4,5–dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and we assessed drug sensitivity by calculating assay area under the curve (AUC) for each agent. The expression of multi‐drug resistance genes (MDR‐1, MRP‐1, MRP‐2) was detected by reverse transcription‐polymerase chain reaction (RT‐PCR). Glutathione (GSH) concentration was measured by an enzymatic assay. Topoisomerase (topo) I activity was assayed in terms of relaxation of supercoiled plasmid substrate DNA. The IC50 to anticancer agents ranged widely. The assay AUC indicated that 3 of 5 cell lines (RMG‐I, RMG‐II, and KK) were sensitive to paclitaxel (PTX), 3 (HAC‐2, RMG‐I, and RMG‐II) were sensitive to 7–ethyl‐10‐hydroxycamptothecin (SN‐38), which is an active metabolite of camptothecin (CPT‐11), and only one (HAC‐2) was sensitive to cisplatin (CDDP). All cell lines were resistant to mitomycin‐C (MMC) and etoposide (VP‐16). The MRP‐1 gene was detected in all cell lines. Only one cell line showed both MRP‐2 and MDR‐1 gene expression. Except for HAC‐2 cells, expression of MRP genes was related to CDDP resistance, and MDR‐1 gene expression was associated with PTX resistance. GSH concentrations increased after exposure to CDDP or MMC in all cell lines. There was a significant correlation between topo‐I enzymatic activity and the response to SN‐38. The present study revealed several resistance mechanisms in CCC and the results suggested that PTX and CPT‐11 might be effective agents to treat CCC.
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DOI：
10.1111/j.1349-7006.1990.tb02602.x
发表时间：
1990-05-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
FUJIWARA, Y;SUGIMOTO, Y;SAIJO, N
通讯作者：
SAIJO, N
DOI：
10.1073/pnas.89.7.3070
发表时间：
1992-04-01
影响因子：
11.1
作者：
GODWIN, AK;MEISTER, A;ANDERSON, ME
通讯作者：
ANDERSON, ME
影响因子：
45.3
作者：
Rose, PG;Blessing, JA;Homesley, HD
通讯作者：
Homesley, HD
影响因子：
4.7
作者：
Goff, BA;delaCuesta, RS;Fuller, AF
通讯作者：
Fuller, AF
DOI：
10.1073/pnas.78.6.3487
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LIU, LF;MILLER, KG
通讯作者：
MILLER, KG