Abstract
Objective: To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0–G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0–G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0–G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0–G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.
Similar content being viewed by others
References
Coukos G, Rubin SC. Chemotherapy resistance in ovarian cancer: New molecular perspectives [J]. Obstet Gynecol 1998; 91: 783.
Hamilton G. Multicellular spheroids as an in vitro tumor model [J]. Cancer Lett 1998; 131: 29.
Kobayashi H, Man S, Graham CH, et al. Acquired multicellular-mediated resistance to alkylating agents in cancer [J]. Proc Natl Acad Sci 1993; 90: 3294.
Carreiras F, Cruet S, Staedel C, et al. Human ovarian adenocarcinoma cells synthesize vitronectin and use it to organize their adhesion [J]. Gynecol Oncol 1999; 72: 312.
Cruet S, Sc M, Salamanca C, et al. α v β 3 and vitronectin expression by normal ovarian surface epithelial cells: Role in cell adhesion and cell proliferation [J]. Gynecol Oncol 1999; 75: 254.
Chen JL, Feng YJ, Li Qink et al. Multicellular-mediated resistance to Cisplatin and Taxol in cells of human ovarian cancer SK-OV-3ip1 multicellular aggregates [J]. Chin Med J, 2001; 114(5):No 2. http://www.cmj.org.
Chen JL, Jiang S, Yang RF, et al. Mechanism of drug resistance and reversal with ligustrazine and cyclosporin A in cisplatin-induced human epithelial ovarian cancer resistant cell line 3Ao/cDDP[J]. Chin J Cancer Res 2000; 13:197.
St. Croix B, florenes VA, Rak JW, et al. Impact of the cyclin-dependent kinase inhibitor P27Kipl on adhesion-dependent resistance of tumor cells to anticancer agents [J]. Nature Med 1996; 2: 1204.
Author information
Authors and Affiliations
Corresponding author
Additional information
Foundation item: This work was supported by the National Natural Science Foundation of China (No. 30000177).
Biography: CHEN Jian-li(1971–), doctor of medicine, attending physician, majors in gynecological oncology.
Rights and permissions
About this article
Cite this article
Chen, Jl., Feng, Yj. & Zhang, Q. Multicellular-mediated expression of P-GP and MRP and relationship with cell cycle profiles in human ovarian cancer SK-OV-3ip1 multicellular aggregates. Chin. J. Cancer Res. 13, 258–261 (2001). https://doi.org/10.1007/s11670-001-0043-7
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11670-001-0043-7