Circumvention of resistance to daunorubicin by N-acetyldaunorubicin in Ehrlich ascites tumor.

نویسنده

  • T Skovsgaard
چکیده

Experimental evidence indicates that Ehrlich ascites tumor cells resistant to daunorubicin (DNR) have a higher active drug extrusion than do wild-type cells. In the present study, the possibility of circumventing this mechanism of resistance by addition of an analog of DNR, N-acetyldaunorubicin (N-acetyl-DNR), was investigated in vitro and in vivo. The affinity of N-acetyl-DNR was 7 times lower than that of DNR in the lysates of both wild-type and resistant cells. In agreement with this finding, N-acetyl-DNR reduced the binding of [3H]DNR to lysate from the two cell lines only to a minor extent. On the other hand, N-acetyl-DNR exerted a marked inhibition on both the active efflux and the unidirectional influx of [3H]DNR in both cell lines. Within certain limits, addition of N-acetyl-DNR resulted in increased steady-state uptake of [3H]DNR; in wildtype cells, the maximal obtainable elevation was 18%, compared to 142% in resistant cells. In vivo addition of N-acetyl-DNR, even at 80 mg/kg for 4 consecutive days, did not influence the toxicity of DNR in mice. In a therapeutic experiment, addition of N-acetyl-DNR increased the antitumor activity of DNR upon the resistant tumor line significantly, but no change was observed in the wild-type tumor. These data indicate that N-acetyl-DNR or related analogs may be used as adjuvants to circumvent acquired resistance to DNR.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Antitumor Activity of Prosopis glandulosa Torr. on Ehrlich Ascites Carcinoma (EAC) Tumor Bearing Mice

The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantl...

متن کامل

Verapamil restoration of daunorubicin responsiveness in daunorubicin-resistant Ehrlich ascites carcinoma.

We have studied the influence of verapamil hydrochloride on the in vitro and in vivo effects of daunorubicin in Ehrlich ascites carcinoma. Daunorubicin-sensitive tumor was rendered resistant to daunorubicin by the continuous treatment of sequential generations of tumor-bearing BALB/c mice. The ability of daunorubicin to inhibit [(3)H]uridine and [(3)H]thymidine incorporation and the effect of d...

متن کامل

Antitumor Activity of Prosopis glandulosa Torr. on Ehrlich Ascites Carcinoma (EAC) Tumor Bearing Mice

The antitumor activity of ethanol extract of Prosopis glandulosa Torr. (EPG) was evaluated against Ehrlich ascites carcinoma (EAC) tumor model in Swiss albino mice on dose dependent manner. The activity was assessed using survival time, average increase in body weight, hematological parameters and solid tumor volume. Oral administration of EPG at the dose of 100, 200 and 400 mg/Kg, significantl...

متن کامل

Investigating the anti-tumoral effect of curcumin on the mice in which Ehrlich ascites and solid tumor is created

Objective(s): In this study, the effects of different doses of curcumin application on Ehrlich ascites tumor (EAT) created in the mice of BALB/c type were investigated.Materials and Methods: Curcumin extracts can have hindering effect on tumor volume, vascular density, EAT cells around the tissues, and can support apoptosis. EAT cells (1x106) received from stock animals were injected intraperit...

متن کامل

Enhancement by cyclosporin A of daunorubicin efficacy in Ehrlich ascites carcinoma and murine hepatoma 129.

Cyclosporin A abrogates pleiotropic drug resistance in certain experimental tumors. Its impact on drug-sensitive tumors has not been investigated. Our studies show that in drug-sensitive Ehrlich ascites carcinoma and hepatoma 129 cyclosporin A enhances daunorubicin inhibition of DNA synthesis in vitro and prolongs survival of host mice in vivo. Of particular interest is that cyclosporin A conve...

متن کامل

ذخیره 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 نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Cancer research

دوره 40 4  شماره 

صفحات  -

تاریخ انتشار 1980