Schedule-dependent antagonism of gemcitabine and cisplatin in human anaplastic thyroid cancer cell lines.
نویسندگان
چکیده
Anaplastic thyroid carcinoma (ATC) affects primarily elderly patients, with a median survival of 4-12 months after diagnosis. Presently, under clinical investigation the combination of cisplatin (CDDP) and gemcitabine (GEM) has promising activity in several of human tumor types. To develop new approaches for therapy of ATC, we evaluated the antineoplastic activity of GEM and CDDP alone (1-h and 24-h drug exposure) or in combination in the ATC cell lines SW1736, 8505C, C643, and HTh74. IC50 values were determined by the sulforhodamine B assay, activity was evaluated by the relative antitumor activity (RAA) and drug interaction assessed by isobologram analysis. GEM seemed to be active in ATC, with RAA ranging from 12-114 and CDDP only modestly active (RAA, 0.24-1.4). In four different drug schedules tested, the drug combination was additive when GEM preceded CDDP exposure (combination index, approximately 1), whereas when CDDP preceded GEM exposure the combination was significantly antagonistic (combination index, >1). In SW1736 and 8505C cells, we observed a strong S phase arrest and DNA synthesis inhibition 24 h after a 1-h exposure to an IC50 of CDDP. On the basis of molecular drug targets, cell cycle arrest points, and DNA synthesis inhibition, a model was developed to explain the interaction observed for the combination of GEM and CDDP. In conclusion, GEM shows promising cytostatic activity in ATC. Interaction of GEM and CDDP was schedule and dose dependent, favoring a regime in which GEM is followed by CDDP. Additionally, our model system suggests that DNA-synthesis inhibition and S phase arrest may be important determinants for the drug interaction between GEM and CDDP.
منابع مشابه
Investigation of selective CDK4/6 inhibitor (Abemaciclib) cytotoxicity effects on human anaplastic thyroid cancer
Background: Thyroid cancer is one of the most common endocrine malignancies. Anaplastic thyroid cancer is a rare and dead full cancer among types of the thyroid cancer. Despite the conventional chemotherapy, a considerable number of the patients show developing chemo resistance. Therefore, there is a necessary need to find the novel therapeutic approaches in the anaplastic thyroid cancer patien...
متن کاملCombined Effect of Iodine Contrast Media, Cisplatin and External Beam Radiotherapy on Anaplastic Thyroid Cancer Cells
Introduction: The current study investigated the combination of high Z atoms (iodine-, platinium-based drugs) with using low energy irradiation (120kvp) in Anaplastic Thyroid cancer cells.Materials and Methods: For this purpose, eight groups were designed: control (CNT), different concentrations of Iodine contrast media (ICM), irradiation with various doses, Cis-platin (CDDP) with different c...
متن کاملComparison of MTT, trypan blue, and clonogenic assay, to determine the viability in human anaplastic thyroid cancer cell line
Background: Evaluation of cell viability is momentous in pharmacologic and oncological research. Cell viability evaluation determines cell sensitivity and consequently treatment outcome. Various methods are available to determine cell survival. Each of these methods evaluates different endpoints. Accordingly, determining the correlation between these methods is important. In this study, in orde...
متن کاملGeneration of Cisplatin-Resistant Ovarian Cancer Cell Lines
Ovarian cancer is the most lethal gynecological cancer in which cisplatin-based treatment plays fundamental role as the first line chemotherapy option. However, development of platinum-resistance is a critical and poorly understood problem in ovarian cancer treatment. Although in vitro generation of platinum-resistant ovarian cancer cell lines is a long established approach to uncover the molec...
متن کاملCytotoxic effect of curcumin on viability and P21 and Bcl-2 genes expression of the human anaplastic thyroid Carcinoma cells line (SW-1736)
Background & Aim: Anaplastic thyroid carcinoma (ATC) is an uncommon malignancy of the thyroid .with poor prognosis and 2 to 6 month of survival time. The aim of this study was to explore the effect of curcumin on bioavailability and expression of p21 and Bcl-2 genes in human anaplastic thyroid carcinoma cell line (SW-1736). Methods: In this study, human anaplastic thyroid carcinoma (SW-1736) c...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Clinical cancer research : an official journal of the American Association for Cancer Research
دوره 6 5 شماره
صفحات -
تاریخ انتشار 2000