Zoledronic acid inhibits proliferation and impairs migration and invasion through downregulating VEGF and MMPs expression in human nasopharyngeal carcinoma cells

Li, Xu‐Yuan; Lin, Yingcheng; Huang, Weiqing; Hong, Chao‐Qun; Chen, Jiongyu; You, Yanjie; Li, Weibing

doi:10.1007/s12032-011-9904-1

Cited by 31 publications

(35 citation statements)

References 23 publications

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“…Our previous study reported that ZOL may impair cancer cell migration and invasion via downregulating vascular endothelial growth factor and matrix metalloproteinase expression (28). Therefore, the aim of the present study was to examine whether this anti-metastatic effect could be augmented by co-treatment with ZOL plus IR.…”

Section: Zol Plus Ir Results In Significant Anti-metastatic Effects Omentioning

confidence: 90%

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

Wang

et al. 2017

Oncology Letters

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Abstract. Radiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer. Although cancer cells are usually sensitive to radiotherapy, metastasis and local failure still occur mainly due to developed resistance to radiotherapy. Thus, it is critical to improve therapeutics for cancer treatment. The present study demonstrated that third-generation bisphosphonate zoledronic acid (ZOL), even at a low concentration, augments the radiosensitivity of cancer cells exposed to ionizing radiation (IR) by inducing S-phase arrest and subsequently promoting apoptosis. This function of ZOL was associated with elevated levels of cyclin A and cyclin B in the S and M phases, as well as decreased p21 CIP1 expression. In addition, ZOL also inhibited malignant the invasiveness of cancer cells. Notably, these effects could be enhanced concurrently with IR. The present data indicated that combined treatment with ZOL plus IR may be a novel technique to augment the radiosensitivity of cancer cells. IntroductionRadiotherapy and adjuvant chemotherapy have become the standard treatments for multiple types of cancer, including esophageal and nasopharyngeal carcinoma (1,2). Although radiotherapy is widely used to treat early-stage tumors, patients with advanced-stage tumors often experience failure of treatment mainly due to resistance to radiotherapy, resulting in recurrence and distant metastases (2-6). Therefore, the development of potent and reliable radiosensitizers is necessary for improving overall treatment outcomes in cancer therapy.Zoledronic acid (ZOL) is a compound containing nitrogen and bisphosphonates, which harbors anti-reabsorption effects (7). ZOL is used as therapy for bone metastasis in malignancy and a number of metabolic disorders, including bone pain, bone fractures and hypercalcaemia (8,9). ZOL inhibits farnesyl pyrophosphate synthase, a key enzyme in the isoprenoid biosynthetic pathway, and prevents prenylation of small guanosine triphosphate-binding proteins, including Rho, p21 ras , cell division cycle 42, Rac and Rab, which are essential for different cellular functions such as signal transduction and cell adhesion (7-9). ZOL is considered to possess antitumor activity, particularly in combination with chemotherapeutic anticancer drugs (10-12). This effect of ZOL could be observed on cancer cells derived from a variety of tumors, including breast, prostate and pancreatic cancers, by inducing cell apoptosis and inhibiting cell invasion, adhesion and angiogenesis (10-13). Currently, numerous patients with bone metastases secondary to a broad range of solid tumors are benefiting from the antitumor effects of ZOL (14).Our previous study demonstrated the synergistic cytotoxic effects of ZOL and ionizing radiation (IR) on esophageal squamous cell carcinoma and endothelial cells (15). Accordingly, combined treatment with ZOL plus IR may be an encouraging method to treat cancer with less side effects and complications, compared with the use of these agents alone (15)(16)(17)(18)(19...

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Section: Zol Plus Ir Results In Significant Anti-metastatic Effects Omentioning

confidence: 90%

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

Wang

et al. 2017

Oncology Letters

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“…The recent use of bisphosphonates was associated with decreased MMP activation [20][21][22]. In addition, bisphosphonates treatment in patients with several types of cancer decreased serum lipid hydroperoxide levels and increased serum glutathione peroxidase levels [23].…”

Section: Introductionmentioning

confidence: 99%

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

Carvalho

Gonçalves

Alegre

et al. 2016

Cell Physiol Biochem

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Background: Cardiotoxicity is the major side effect of doxorubicin. As mechanisms that are involved in cardiotoxicity are ambiguous, new methods for attenuating cardiotoxicity are needed. Recent studies have shown that bisphosphonates can decrease oxidative stress. Therefore, the objective of this study was to evaluate the effect of pamidronate on preventing acute doxorubicin-induced cardiotoxicity. Methods: Sixty-four male Wistar rats were allocated into four groups: the control group (C), the pamidronate group (P), the doxorubicin group (D) and the doxorubicin/pamidronate group (DP). The rats in the P and DP groups received pamidronate injections (3 mg/kg, IP). After 24 hours, the rats in the D and DP groups received doxorubicin injections (20 mg/kg, IP). Forty-eight hours after doxorubicin injection, the rats were killed. Echocardiography, isolated heart study and biochemical analysis were performed. Results: Doxorubicin-induced acute cardiotoxicity showed increased matrix metalloproteinases (MMP)-2 activation, oxidative damage and induced alterations in myocardial energetic metabolism. Pamidronate did not inhibit MMP-2 activation but attenuated oxidative stress and improved myocardial energetic metabolism. Regarding cardiac function, the DP group exhibited a decrease in the left ventricular ejection fraction in the echocardiography and a decrease in +dP/dt in the isolated heart study compared with other groups. The same DP group presented serum hypocalcaemia. Conclusions: Despite its ability to reduce oxidative stress and improve energy metabolism in the heart, pamidronate worsened systolic function in rats treated with doxorubicin, and therefore we cannot recommend its use in conjunction with anthracycline chemotherapy.

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“…Recent studies also showed that doxycycline inhibited activity of gelatinases and diminished tumor growth, invasion and metastasis in osteosarcoma, and lung, ovarian, cervical and oral cancer cell lines [39][40][41][42]. Similarly, zoledronate, which is nitrogen-containing bisphosphonate, exerts antitumoral effects by suppressing MMP expression and/or activity in various cancers [43,44]. Recently, we have also reported that zoledronate downregulated MMP-2 and -9 expression and activities in PC3 prostate cancer cells [45].…”

Section: Discussionmentioning

confidence: 89%

Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

Ogut

Reel

Korkmaz

et al. 2017

Folia Histochem Cytobiol.

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Introduction. Matrix metalloproteinase enzymes (MMPs) play important role in inflammation, malignant cell proliferation, invasion and angiogenesis by mediating extracellular matrix degradation. Doxycycline, a synthetic tetracycline, behaves as a MMP inhibitor at a subantimicrobial dose and inhibits tumor cell proliferation, invasion and angiogenesis. The aberrant activity of nuclear factor kappa B (NF-kB) causes activation of MMPs and thereby proliferation and invasion of cancer cells. The aim of this study was to investigate the effects of doxycycline on the expression of MMPs in lipopolysaccharide (LPS)-induced PC3 human prostate cancer cells and the possible role of NF-kB signaling. Material and methods. PC3 cells were incubated with LPS (0.5 µg/mL) for 24 h in the presence or absence of doxycycline (5 µg/mL). The effects of LPS and doxycycline on the expressions of MMP-2, MMP-8, MMP-9, MMP-10, NF-kB/p65, IkB-a, p-IkB-a, IKK-b were examined by Western blotting and immunohistochemistry in PC3 cells. Furthermore, relative proteinase activities of MMP-2 and MMP-9 were determined by gelatin zymography. Results. LPS increased expression and activity of MMP-9 and expression of MMP-8, MMP-10, NF-kB/p65, p-IkB-a, IKK-b and doxycycline down-regulated its effects with the exception of MMP-10 expression. The expression of MMP-2 and IkB-a was affected by neither LPS nor doxycycline. Conclusions. Our findings indicate that doxycycline inhibits the expression of various MMPs and NF-kB signaling may play a role in the regulation of MMPs expression in LPS-induced PC3 human prostate cancer cells.

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Zoledronic acid inhibits proliferation and impairs migration and invasion through downregulating VEGF and MMPs expression in human nasopharyngeal carcinoma cells

Cited by 31 publications

References 23 publications

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

Zoledronic acid augments the radiosensitivity of cancer cells through perturbing S- and M-phase cyclins and p21CIP1 expression

Pamidronate Attenuates Oxidative Stress and Energetic Metabolism Changes but Worsens Functional Outcomes in Acute Doxorubicin-Induced Cardiotoxicity in Rats

Doxycycline down-regulates matrix metalloproteinase expression and inhibits NF-κB signaling in LPS-induced PC3 cells

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