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Octreotide neutralizes dexamethasone antitumor actions on P388 murine lymphocytic leukemia in vivo
D T P Trafalis1, E Chrysogelou, P Dalezis
11st Department of Medical Oncology, "Metaxa" Cancer Hospital, Piraeus, Greece.
Purpose:
A wide variety of human malignancies, including lymphoproliferative neoplasms, express somatistatin (SS) receptors (SS-R). SS induces apoptosis and exerts pronounced antiproliferative effects on various human tumors cell lines, human xenografts, and animal tumors including P388 lymphocytic leukemia. In patients with thymoma the combination of octreotide (OCT) with corticosteroids improves the overall response rate. It has been reported that SS can increase glucocorticoid activity. Hereby, we studied the in vitro and in vivo activity of the SS analogue OCT and of the glucocorticoid dexamethasone (DEX) alone or in combination against the murine P388 lymphocytic leukemia.
Materials And Methods:
Cultures of P388 lymphocytic leukemia and BDF(1) male mice implanted with P388 cells where used for the in vitro an in vivo evaluation of the antileukemic activity of SS and DEX.
Results:
OCT induced a moderate and DEX a satisfactory cytostatic effect in vitro. OCT produced borderline antileukemic effect when administered on days 1-5 while DEX was effective in all schemes and routes of administration. However, none of the combination schemes exerted any anti-leukemic activity both in vitro and in vivo.
Conclusion:
Since both SS and glucocorticoids exert direct (via receptors) and indirect antitumor actions (regulation of growth factor activity) on several cell lines, in vitro and in vivo, it becomes obvious that further in vitro studies shall provide the molecular evidence for the signal transduction pathways which are involved in the interactions of such important anticancer drugs. Based on the results of the present study, the simultaneous use of these drugs in clinical practice should be carefully considered.
Insights
Somatostatin (SS) analogue octreotide (OCT) and dexamethasone (DEX) showed individual anticancer effects against P388 leukemia in vitro and in vivo. However, combining OCT and DEX did not improve antileukemic activity, suggesting careful consideration for simultaneous clinical use.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Somatostatin receptors (SS-R) are expressed in various human malignancies.
- Somatostatin (SS) exhibits antiproliferative and pro-apoptotic effects on tumors.
- Combination therapy of octreotide (OCT) and corticosteroids shows improved response rates in thymoma patients.
Purpose of the Study:
- To investigate the in vitro and in vivo antileukemic activity of SS analogue OCT and glucocorticoid dexamethasone (DEX).
- To evaluate the efficacy of OCT and DEX alone and in combination against murine P388 lymphocytic leukemia.
Main Methods:
- In vitro studies using P388 lymphocytic leukemia cell cultures.
- In vivo studies using BDF(1) male mice implanted with P388 cells.
- Evaluation of antileukemic activity of SS analogue OCT and DEX, alone and in combination.
Main Results:
- OCT demonstrated moderate and DEX satisfactory cytostatic effects in vitro.
- DEX was effective against P388 leukemia in all tested schemes and routes of administration in vivo.
- Combination therapy of OCT and DEX showed no enhanced antileukemic activity in vitro or in vivo.
Conclusions:
- Further in vitro studies are needed to elucidate the molecular mechanisms of SS and glucocorticoid interactions.
- The signal transduction pathways involved in the interaction of these anticancer drugs require detailed investigation.
- Simultaneous administration of SS analogues and glucocorticoids in clinical practice warrants careful consideration based on current findings.
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