Antitumorigenic Effect of Tramadol and Synergistic Effect With Doxorubicin in Human Breast Cancer Cells

Abstract

BackgroundBreast cancer in women is one of the leading causes of cancer mortality worldwide, and curative therapy is the main focus of clinical treatment. Anesthetic-analgesic techniques might alter stress responses and immunity and thereby influence outcomes in cancer patients. This study investigated the effect of tramadol on breast cancer progression and metastasis.MethodsThe effects of tramadol on two different subtypes of human breast adenocarcinoma cell lines, MDA-MB-231 and MCF-7, were studied with regard to cell growth, migration, colony formation and invasion and normoxic or hypoxic microenvironment for the expression of hypoxia-inducible factor-1α, reactive oxygen species, epithelial-mesenchymal transition related and cyclin-related proteins. The co-administration of tramadol and doxorubicin was studied to determine whether the effective doxorubicin dose might be reduced in combination with tramadol.ResultsThe results showed that tramadol inhibited cell growth at concentrations more than 0.5 and more than 1.0 mg/mL in MDA-MB-231 and MCF-7 cells, respectively. Additionally, cell migration, colony formation and invasion were inhibited in a dose-dependent manner by tramadol in both cell lines. The combination of tramadol and doxorubicin induced synergistic effects in MDA-MD-231 cells and, with specific dosage combinations in MCF-7 cells.ConclusionsTramadol may regulate epithelial-mesenchymal transition and possess cytotoxic effects in breast cancer cells. Tramadol inhibits the progression of breast cancer cells and might be a candidate for combination therapy, especially for triple-negative breast cancer, and is a promising treatment strategy for breast cancer.

Breast cancer and neurotransmitters: emerging insights on mechanisms and therapeutic directions

“…Exercise [107,108] Stress [4,7,[108][109][110][111] Meditation [111][112][113] Gut microbiota [114,115] Smoking [53][54][55][56] On the other hand, the opioid analgesic tramadol could inhibit proliferation, migration, and invasion of breast cancers by inactivating the α2-adrenoceptor signaling pathway [50]. Based on cellular experiments, Huang et al concluded that tramadol inhibits the progression of breast cancer cells and should be investigated further for use in combination therapy, especially for triple-negative breast cancer [51]. Like tramadol, the α2-adrenoceptor antagonist rauwolscine also suppressed tumor growth, in mice with human breast cancer cells [52].…”

Bacterial extracellular vesicles: A position paper by the microbial vesicles task force of the Chinese society for extracellular vesicles

“…98 The biofilm composite nano-drug delivery system (OMVs-MSN-5-FU) has also been confirmed to have good anti-tumor effect in lymph node metastasis from oral squamous cell carcinoma. 99 In a recent study, BEVs were used to co-load paclitaxel (PTX) and regulate the expression of DNA damage response 1 (Redd1)-siRNA, thereby suppressing tumor growth and modulating the tumor metabolism microenvironment. The siRNA@M-/PTX-CA-OMVs developed in this study were able to release PTX in response to the acidic tumor microenvironment (pH 6.8) in a triplenegative breast cancer model.…”

“…Affected by DOX‐OMVs, macrophages are recruited in the tumor microenvironment and perform a synergistic antitumor effect with the OMVs 98 . The biofilm composite nano‐drug delivery system (OMVs‐MSN‐5‐FU) has also been confirmed to have good anti‐tumor effect in lymph node metastasis from oral squamous cell carcinoma 99 . In a recent study, BEVs were used to co‐load paclitaxel (PTX) and regulate the expression of DNA damage response 1 (Redd1)‐siRNA, thereby suppressing tumor growth and modulating the tumor metabolism microenvironment.…”

Pancreatic Cancer and Microenvironments: Implications of Anesthesia

“…In a xenograft mouse model, Kim et al showed that a clinical dose of tramadol had antitumor effects on MCF-7-cell-derived breast cancer [ 171 ]. In addition, tramadol may regulate EMT and exert cytotoxic effects in breast cancer cells [ 172 ]. However, literature on tramadol in PC progression is lacking, and further laboratory studies are required.…”