Theophylline administration markedly reduces hepatic and pulmonary implantation of B16-F10 melanoma cells in mice

被引:19
作者
Lentini, A
Vidal-Vanaclocha, F
Facchiano, F
Caraglia, M
Abbruzzese, A
Beninati, S
机构
[1] Univ Roma Tor Vergata, Dept Biol, I-00133 Rome, Italy
[2] Univ Basque Country, Dept Cellular Biol & Morphol Sci, Leioa, Vizcaya, Spain
[3] Ist Dermopatico Immacolata, Lab Vasc Pathol, Rome, Italy
[4] Univ Naples Federico II, Dept Biochem & Biophys, Naples, Italy
关键词
melanoma cells; metastasis; methylxanthines;
D O I
10.1097/00008390-200010000-00005
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Theophylline-treated B16-F10 melanoma cells show a lower experimental metastatic potential in vivo. To identify the possible mechanism(s) involved and on the basis of previous reports, we tested the induction of apoptosis in B16-F10 cells. Fluorescence activated cell sorter (FACS) analysis and p53 overexpression in theophylline-treated B16-F10 melanoma cells appeared to suggest enhanced cell death by apoptosis. The in vivo effects of orally administered theophylline in mice were investigated using different treatment schedules in mice that had undergone hepatic or pulmonary colonization with tumour cells, Mice received theophylline in their drinking water according to different protocols: (i) from 3 days before tumour cell inoculation until animal sacrifice ('early treatment'); (ii) from 3 days before until 3 days after tumour cell inoculation ('short treatment'); or (iii) from 3 days after tumour cell inoculation until animal sacrifice ('late treatment'). In the 'early treatment' group, the number of melanoma foci was reduced by 92.3% in the liver and 81.4% in the lung compared with control animals (P<0.001). In the 'short treatment' group, there was an 80.2% and 72.2% reduction in liver and lung metastases, respectively (P< 0.001). In the 'late treatment' group, the inhibition of metastasis was 59.7% for liver and 45.3% for lung (P<0.005). Survival studies showed that 50% of the 'early' theophylline-treated animals died 33.2 +/- 2.0 days after intrasplenic injection (control group: 23.1 +/- 1.8 days; P<0.001) and 33.9 +/- 2.5 days after tail vein injection (control group: 24.1 +/- 1.4 days; P< 0.001). Taken together, these observations provide useful information for the potential clinical application of theophylline as a chemotherapeutic agent against malignant melanoma. (C) 2000 Lippincott Williams & Wilkins.
引用
收藏
页码:435 / 443
页数:9
相关论文
共 44 条
  • [1] ALBINI A, 1987, CANCER RES, V47, P3239
  • [2] Alford D, 1998, BIOCHEM SOC SYMP, P245
  • [3] Arany I, 1997, ANTICANCER RES, V17, P4607
  • [4] Autuori F, 1998, Adv Biochem Eng Biotechnol, V62, P129, DOI 10.1007/BFb0102308
  • [5] BARBERAGUILLEM E, 1991, MICROCIRCULATION CAN, P183
  • [6] Benedetti L, 1996, BLOOD, V87, P1939
  • [7] DIFFERENCES IN THE POSTTRANSLATIONAL MODIFICATION OF PROTEINS BY POLYAMINES BETWEEN WEAKLY AND HIGHLY METASTATIC B16 MELANOMA-CELLS
    BENINATI, S
    ABBRUZZESE, A
    CARDINALI, M
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1993, 53 (05) : 792 - 797
  • [8] BENINATI S, 1993, RETINOIDS PROGR RES, P341
  • [9] GENETICS, DEVELOPMENT, AND MALIGNANCY OF MELANOCYTES
    BENNETT, DC
    [J]. INTERNATIONAL REVIEW OF CYTOLOGY - A SURVEY OF CELL BIOLOGY, VOL 146, 1993, 146 : 191 - 260
  • [10] BERGSTRAND H, 1980, EUR J RESPIR DIS, V61, P37