Harvard University. US: Some NSAIDs can stem the growth of a common intracranial tumor. Researchers from the Harvard-MIT Program in Speech and Hearing Bioscience and Technology
and Massachusetts Eye and Ear have demonstrated that salicylates, a
class of nonsteroidal inflammatory drugs (NSAIDs), reduced the
proliferation and viability of cultured vestibular schwannoma cells that
cause a sometimes lethal intracranial tumor that typically causes
hearing loss and tinnitus.
The research is described online in Translational Research.
“These preclinical data based on cultured primary vestibular
schwannoma cells, combined with our previously published work on aspirin
intake correlating with halted growth of vestibular schwannomas (also
known as acoustic neuroma), motivate a future prospective clinical
trial,” said Konstantina Stankovic,
HMS assistant professor of otology and laryngology and principal
investigator at the Eaton-Peabody Laboratories at Mass Eye and Ear.
Vestibular schwannomas are the most common tumors of the
cerebellopontine angle and the fourth most common intracranial tumors.
Although vestibular schwannomas are histologically nonmalignant, they
can lead to substantial morbidity, including sensorineural hearing loss,
vestibular dysfunction and facial nerve paralysis. Large vestibular
schwannomas can cause additional paralysis of other cranial nerves,
brainstem compression and death, the authors write.
Currently, patients with symptomatic or growing vestibular
schwannomas can undergo surgical resection or radiotherapy. Both of
these procedures can result in serious complications. Effective drug
therapies that can limit growth would greatly advance health care for
these patients.
Salicylates are attractive therapeutics because they are clinically
relevant, well tolerated and commonly used against pathologies such as
pain and arthritis. Furthermore, in some cases, chronic intake of
salicylates has led to a significant reduction in the incidence and
burden of various tumors, such as colorectal cancer.
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“In our study, we focused on salicylates because a mechanism of their
action is inhibition of cyclooxygenase 2 (COX-2), and a previous study
reported that immunohistochemical expression of COX-2 correlated with
vestibular schwannoma growth rates. We assessed the efficacy of three
different salicylates against vestibular schwannoma: aspirin, sodium
salicylate (NaSal) and 5-aminosalicylic acid (5-ASA),” Stankovic said.
The team found COX-2 to be aberrantly expressed in human vestibular
schwannomas and primary human vestibular schwannoma cells in comparison
to control human nerve specimens and primary Schwann cells (SCs),
respectively. Further, levels of prostaglandin E2, the downstream
enzymatic product of COX-2, correlated with the primary vestibular
schwannoma culture proliferation rate. Changes in proliferation, cell
death and cell viability were analyzed in primary vestibular schwannoma
cultures treated with aspirin, NaSal or 5-ASA. These drugs decreased
proliferation and viability of vestibular schwannoma cells without
increasing cell death or affecting healthy schwannoma cells. The
cytostatic effect of aspirin in vitro was consistent with Stankovic’s
previous clinical finding that vestibular schwannoma patients taking
aspirin demonstrate reduced tumor growth.
”Overall, this work suggests that COX-2 is a key modulator in
vestibular schwannoma cell proliferation and survival and highlights
salicylates as promising pharmacotherapies against vestibular
schwannoma,” the authors concluded.
This study was supported by the National Institute on Deafness and
Other Communication Disorders grants T32 DC00038 and K08DC010419, the
Bertarelli Foundation and Department of Defense grant W81XWH-14-1-0091.
Adapted from a Mass Eye and Ear news release.