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Combining Anti-Mir-155 with Chemotherapy for the Treatment of Lung Cancers
Ist Teil von
Clinical cancer research, 2017-06, Vol.23 (11), p.2891-2904
Ort / Verlag
United States: American Association for Cancer Research Inc
Erscheinungsjahr
2017
Link zum Volltext
Quelle
Free E-Journal (出版社公開部分のみ）
Beschreibungen/Notizen
The oncogenic miR-155 is upregulated in many human cancers, and its expression is increased in more aggressive and therapy-resistant tumors, but the molecular mechanisms underlying miR-155-induced therapy resistance are not fully understood. The main objectives of this study were to determine the role of miR-155 in resistance to chemotherapy and to evaluate anti-miR-155 treatment to chemosensitize tumors.
We performed
studies on cell lines to investigate the role of miR-155 in therapy resistance. To assess the effects of miR-155 inhibition on chemoresistance, we used an
orthotopic lung cancer model of athymic nude mice, which we treated with anti-miR-155 alone or in combination with chemotherapy. To analyze the association of miR-155 expression and the combination of miR-155 and
expression with cancer survival, we studied 956 patients with lung cancer, chronic lymphocytic leukemia, and acute lymphoblastic leukemia.
We demonstrate that miR-155 induces resistance to multiple chemotherapeutic agents
, and that downregulation of miR-155 successfully resensitizes tumors to chemotherapy
We show that anti-miR-155-DOPC can be considered non-toxic
We further demonstrate that miR-155 and
are linked in a negative feedback mechanism and that a combination of high expression of miR-155 and low expression of
is significantly associated with shorter survival in lung cancer.
Our findings support the existence of an miR-155/TP53 feedback loop, which is involved in resistance to chemotherapy and which can be specifically targeted to overcome drug resistance, an important cause of cancer-related death.
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