Abstract
Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.
Highlights
Salivary adenoid cystic carcinoma (SACC) is a malignant tumor that arises from the secretory epithelial cells of salivary glands
Treatment with Zoledronic acid (ZOL) significantly reduced SACC-83 cell numbers compared with the control cells
To further test the cytotoxic potential of ZOL, cells were incubated with a range of concentrations of ZOL followed by a Cell Counting Kit-8 (CCK-8) test to determine their viability
Summary
Salivary adenoid cystic carcinoma (SACC) is a malignant tumor that arises from the secretory epithelial cells of salivary glands. It accounts for less than 1% of all head and neck malignancies and approximately 10–20% of all salivary neoplasms [1,2,3]. About 40–60% of SACC patients develop distant metastases [5]. Lung is the most common distant metastasis site, followed by bone and other sites including liver, brain, thyroid, spleen and pancreatic gland [5,6,7]. SACC is currently incurable and most patients will eventually succumb to local recurrence, distant metastases or both [7]. The course of the disease is usually fulminant if metastases occur in bone, especially in the spine [7,8]
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